GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5056-5056
    Abstract: Melanoma is an aggressive skin cancer of melanocytic origin characterized by high metastatic potential and mutation rate. Affording a survey of the wide breadth of genomic lesions found in melanoma, we present here an analysis of the somatic mutations discovered in the sequenced exomes of 121 melanoma tumor-normal pairs. We identify frequent genomic alterations both in genes previously implicated in melanoma (BRAF, NRAS, TP53, CDKN2A, PTEN) as well as in several genes whose role in melanoma tumorigenesis has not yet been established and thus are of particular interest. To do so we implement a novel method to increase the identification of genes that are significantly recurrently mutated in melanoma in the setting of its exceptionally high mutation rate. A preponderance of C & gt;T transitions (∼85%) in the observed mutational profile reflects a history of DNA damage due to UV radiation, though the majority of somatic mutations in known melanoma genes are not C & gt;T events. Our study broadens understanding of the genomic lesions involved in melanoma tumorigenesis, and we expect our analysis approach to inform future genomic studies of cancer lineages with similarly high mutation rates. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5056. doi:1538-7445.AM2012-5056
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1139-1139
    Abstract: Prostate cancer is the most common type of cancer diagnosed among men in the United States, accounting for 200,000 new cases and 27,000 deaths per year. Prior genetic studies have shown that chromosomal rearrangements comprise a major mechanism of oncogene activation in prostate cancer. For example, androgen-regulated gene fusions involving ETS family transcription factors are present in the majority of prostate cancers, yet the full repertoire of genomic alterations driving prostate carcinogenesis and progression remains unknown. Toward this end, recent technological advances have made it possible to characterize the full complement of somatic mutations in a single tumor through whole genome sequencing. We are using massively parallel sequencing technology to characterize the complete genomes of several primary prostate adenocarcinomas at & gt;30x coverage. All samples are high-grade primary tumors (Gleason grade 7 to 9) and include cases with and without known ETS family translocations. For each tumor, we are also obtaining & gt;30x sequence coverage of matched normal DNA from blood of these same patients in order to determine the somatic component of the overall variation we observe. Our results indicate that translocations and other chromosomal rearrangements occur frequently in prostate cancer, at a rate of & gt;100 per genome. Further, we have discovered many nonsynonymous sequence mutations (point mutations and indels) in each tumor, some of which may represent novel candidate drivers of tumor progression. The overall rate of somatic point mutations is approximately 1 per Megabase. Integrated analysis of all genomes reveals both recurrent and private alterations. Together, these results illuminate potential avenues for target discovery and demonstrate the unparalleled value in performing complete genome sequencing in this malignancy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1139.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4601-4601
    Abstract: The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of alterations across the entire genome has not been profiled extensively in this disease. We sequenced the genomes of 55 primary prostate tumors and matched normal tissues to catalogue somatic alterations and to study how they accumulate during oncogenesis and progression. By implementing an algorithm to identify genomic alterations that arise together, we found abundant sets of DNA rearrangements and deletions that may occur simultaneously in a single cell. This phenomenon, which we term “chromoplexy," frequently accounts for the dysregulation of prostate cancer genes including PTEN, NKX3-1, TP53 and CDKN1B. The somatic fusion of TMPRSS2 and ERG, which occurs in approximately half of prostate cancers, predominantly arises with additional genomic rearrangements in the context of chromoplexy. We further demonstrate that TMPRSS2-ERG fusion-positive tumors display a unique profile of chromoplexy, with complex chains of rearrangements that may fuse DNA from four or more distinct chromosomes. In prostate cancer and other neoplasms, chromoplexy induces considerable genomic derangement in a series of relatively few events. In several instances, multiple cancer genes from non-contiguous regions of the genome appear to be disrupted simultaneously by this process, suggesting a model of punctuated progression during cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we constructed a path of oncogenic events along which chromoplexy drives prostate carcinogenesis. Citation Format: Sylvan C. Baca, Davide Prandi, Michael S. Lawrence, Juan Miguel Mosquera, Alessandro Romanel, Yotam Drier, Kyung Park, Naoki Kitabayashi, Theresa Y. MacDonald, Eliezer Van Allen, Gregory V. Kryukov, Jean-Philippe Theurillat, T. David Soong, Elizabeth Nickerson, Daniel Auclair, Ashutosh Tewari, Himisha Beltran, Robert C. Onofrio, Gunther Boysen, Candace Guiducci, Christopher E. Barbieri, Kristian Cibulskis, Andrey Sivachenko, Scott L. Carter, Douglas Voet, Gordon Saksena, Michelle R. Cipicchio, Kristin Ardlie, Philip W. Kantoff, Michael F. Berger, Stacey B. Gabriel, Todd R. Golub, Matthew Meyerson, Eric S. Lander, Olivier Elemento, Gad Getz, Francesca Demichelis, Mark A. Rubin, Levi A. Garraway. Punctuated evolution of prostate cancer genomes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4601. doi:10.1158/1538-7445.AM2013-4601
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3925-3925
    Abstract: Prostate cancer is the second most common cause of male cancer deaths in the United States, accounting for 200,000 new cases and 32,000 deaths per year. Chromosomal rearrangements comprise a major mechanism driving prostate carcinogenesis. For example, recurrent gene fusions that render ETS transcription factors under the control of androgen-responsive promoters are present in the majority of prostate cancers. Other types of somatic alterations, such as base substitutions, small insertions/deletions, and chromosomal copy number alterations, have also been described, yet the full repertoire of genomic alterations that underlie primary human prostate cancer remains incompletely characterized. We present here the most comprehensive genome sequencing effort in prostate cancer reported to date. We have characterized the complete genomes of 7 primary prostate cancers and patient-matched normal samples using massively parallel sequencing technology. We observed a mean mutation frequency of 0.9 per megabase, consistent with what has been reported for other tumor types. However, our results indicate that translocations and other chromosomal rearrangements are far more common than expected, with a median of 90 per prostate cancer genome. Several tumors contained chains of balanced rearrangements involving multiple loci associated with known cancer genes. We observed a striking and unexpected relationship between rearrangement breakpoints and chromatin structure, which differed for tumors harboring the ETS gene fusion TMPRSS2-ERG and tumors lacking ETS fusions. We also observed an enrichment of point mutations near rearrangement breakpoints. Three of seven tumors contained rearrangements that disrupted CADM2, a nectin-like member of the immunoglobulin-like cell adhesion molecules; recurrent CADM2 rearrangements were also detected in an independent cohort by fluorescent in situ hybridization (FISH). Four tumors harbored rearrangements disrupting either PTEN, a prostate tumor suppressor, or MAGI2, a PTEN interacting protein not previously implicated in prostate cancer. Together, these results illuminate potential avenues for target discovery and reveal the potential of complex rearrangements to engage prostate tumorigenic mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3925. doi:10.1158/1538-7445.AM2011-3925
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4017-4017
    Abstract: Characterizing the genomic evolution of cancer is critical to understanding disease progression and identifying potential therapeutic targets. By examining the clonal hierarchy of genomic lesions in common tumors, it would be possible to reconstruct the path of oncogenic events that drive carcinogenesis. Reliable assessment of such paths from high-throughput genome sequencing data is complicated by the admixture of normal DNA in tumor samples and by reduced data signal for highly subclonal events. We introduce an approach that exploits individuals’ genetic background by using the abundant germline SNP genotype data provided by whole genome sequence coverage to assess the clonality of genomic alterations, including copy number changes, rearrangements, and point mutations. We developed a novel algorithm, CLONET (CLONality Estimate in Tumors), which analyzes patient-specific heterozygous SNP loci (informative SNPs) and mono-allelic somatic deletions to assess levels of stromal DNA admixture and infer the clonal status of each aberration. For every mono allelic deletion, CLONET assesses the allelic fractions of informative SNPs to determine the apparent proportion of normal cells DNA. Next, through a conservative use of simulation-based error estimates, deletions with the lowest proportions of normal DNA reads are considered clonal. For point mutations, the tumor allelic fraction is corrected for stromal DNA admixture level and subclonality is inferred when it differs significantly from the expected value for clonal lesions. Similarly, the proportions of reads that span each side of a putative breakpoint involved in a rearrangement are matched against the expected values. CLONET also addresses tumor aneuploidy by searching for chromosomes with coverage and allelic fractions of informative SNPs not consistent with a diploid genome. CLONET was tested on 55 whole genome sequences from prostate cancers, a highly heterogeneous tumor type, to catalogue the accumulation of somatic alterations during oncogenesis and progression. In 98% of the cases CLONET made confident assessment of admixture and clonality. We observed consistent clonal lesions involving NKX3-1, the 3Mb region between TMPRSS2 and ERG and FOXP1, as well as early point mutations in SPOP and FOXA1. Overall, we observed a higher rate of subclonal protein-coding point mutation versus deletions (p-value & lt; 10−7). We validated this approach by IHC and FISH for predicted clonal and sub-clonal events. A predicted subclonal homozygous deletion of CHD1 was confirmed by FISH that demonstrated the presence of both nuclei with homozygous and with hemizygous deletion of CHD1. Finally, to assess the general validity of CLONET, we analyzed data from 53 additional tumor genomes, including 25 melanomas and 28 lung adenocarcinomas. In summary, our results imply the existence of consensus paths of tumor carcinogenesis that favor dysregulation of cancer genes in a defined sequence. Citation Format: Davide Prandi, Sylvan C. Baca, Michael S. Lawrence, Juan Miguel Mosquera, Alessandro Romanel, Yotam Drier, Kyung Park, Naoki Kitabayashi, Theresa Y. MacDonald, Eliezer Van Allen, Gregory V. Kryukov, Jean-Philippe Theurillat, T. David Soong, Elizabeth Nickerson, Daniel Auclair, Ashutosh Tewari, Himisha Beltran, Robert C. Onofrio, Gunther Boysen, Candace Guiducci, Christopher E. Barbieri, Kristian Cibulskis, Andrey Sivachenko, Scott L. Carter, Gordon Saksena, Douglas Voet, Alex H. Ramos, Wendy Winckler, Michelle Cipicchio, Kristin Ardlie, Philip W. Kantoff, Michael F. Berger, Stacey B. Gabriel, Todd R. Golub, Matthew Meyerson, Eric S. Lander, Olivier Elemento, Gad Getz, Francesca Demichelis, Mark A. Rubin, Levi A. Garraway. Dissecting the clonal hierarchy of cancer-driving genomic lesions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4017. doi:10.1158/1538-7445.AM2013-4017
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 23_Supplement ( 2015-12-01), p. PR04-PR04
    Abstract: Background: Brain metastases are associated with a dismal prognosis. There is a limited understanding of the oncogenic alterations harbored by brain metastases and whether these are shared with their primary tumors. Our objectives were to (1) elucidate the evolutionary patterns leading to brain metastases and (2) identify whether brain metastases are genetically distinct from their primary tumors and other distal metastatic sites. Methods: We performed whole-exome sequencing of 104 matched brain metastases, primary tumors and normal tissue, including 7 cases with spatially and temporally separated brain metastasis sites and 8 cases with additional extracranial disease sites, including regional lymph nodes, and distal metastases. We developed novel computational tools to perform an integrative analysis of somatic mutations and copy-number alterations. This analysis allowed us to estimate the clonal architecture of the primary and metastases, and to reconstruct a phylogenetic tree relating the subclones from each patient. Results: In all related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found clinically actionable driver alterations in the brain metastases that were not detectable in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were more genetically homogenous and shared nearly all driver alterations detected. Extracranial metastases and regional lymph nodes were highly divergent from brain metastases. Several clinically actionable pathways were enriched in brain metastases. Conclusions: These observations demonstrate that brain metastasis tissue provides an opportunity to identify clinically important driver alterations that may be undetected in single samples of primary tumors, regional lymph nodes, or extracranial metastases. Genetic divergence between primary tumors and brain metastases may underlie some of the difficulties encountered with the combined treatment of systemic disease and brain metastases in patients. When clinically feasible, genomic characterization of brain metastasis tissue should be considered when selecting therapeutic agents for patients with brain metastases. Citation Format: Priscilla K. Brastianos, Scott L. Carter, Sandro Santagata, Daniel Cahill, Amaro Taylor-Weiner, Robert T. Jones, Eliezer Van Allen, Peleg Horowitz, Keith L. Ligon, William T. Curry, Ian F. Dunn, Paul Van Hummelen, Matthew Meyerson, Levi Garraway, Josep Tabernero, Joan Seoane, Stacey Gabriel, Eric S. Lander, Rameen Beroukhim, Tracy T. Batchelor, Jose Baselga, David N. Louis, William C. Hahn, Gad Getz. Genomic characterization of brain metastases reveals branched evolution and metastasis-specific mutations. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr PR04.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. PD8-01-PD8-01
    Abstract: Background: The Metastatic Breast Cancer Project (MBCproject) is a research study that directly engages patients (pts) through social media and advocacy groups, and empowers them to share their samples, clinical information, and experiences. The goal is to create a publicly available dataset of linked genomic, clinical, and pt-reported data to enable research. Methods: In collaboration with pts, advocates, and advocacy groups, a website (MBCproject.org) was developed that allows pts with metastatic breast cancer (MBC) anywhere in the U.S. or Canada to register. Registered pts are sent an online consent form that asks for permission to obtain and analyze their medical records and samples. Once enrolled, pts are sent a saliva kit and a blood kit and asked to mail back a saliva sample, which is used to extract germline DNA, and/or a blood sample, which is used to extract germline DNA and cell free DNA (cfDNA). We contact participants’ medical providers and obtain medical records and a portion of their stored tumor biopsies. Whole exome sequencing (WES) is performed on tumor DNA, germline DNA, and cfDNA; transcriptome sequencing (RNA-seq) is performed on tumor RNA. Medical records and pt-reported data are abstracted to create a detailed clinical record for each pt. All de-identified data are shared regularly via public databases (cbioportal.org, mbcproject.org, dbGaP, NCI Genomic Data Commons) without restrictions. Study updates are shared with participants regularly. Results: From 10/20/15-7/8/19, 5357 women and men with MBC registered. 3290 pts receiving care at over 1700 different institutions consented to share medical records and tumor/saliva/blood samples, and to have genomic analysis performed. Details of clinical data collection, biospecimen acquisition, and genomic data generation to date are outlined in the Table. WES from 463 tumors obtained from 326 pts have been generated (with matched germline WES), including 61 pts with 2 timepoints, 19 pts w 3 timepoints, and 11 pts w 4+ timepoints. 278 tumor exomes were from the breast/regional lymph nodes, 63 from distant metastatic sites and 122 from cfDNA. 110 tumor exomes were from samples obtained before the diagnosis of MBC, 258 from after the diagnosis of MBC, and 95 to be determined (TBD). 161 tumor exomes were obtained prior to any therapy, 204 following some therapy, and 98 TBD. Clinically annotated genomic data are used to study specific pt cohorts (including rare subsets and outliers) and to identify mechanisms of response and resistance to therapies. Examples of the clinical and genomic analyses that will be presented include: - Pts diagnosed & lt;40 yrs of age (1108 pts enrolled; 120 with tumor WES) - de novo MBC (1122 pts enrolled; 121 with tumor WES) - Late recurrence, & gt;5 yrs after diagnosis (830 pts enrolled; 77 with tumor WES) - Long-term survivors, & gt;10 yrs with MBC (159 pts enrolled; 11 with tumor WES) - Resistance to CDK4/6 inhibitors (709 pts enrolled; 148 with tumor WES) Conclusions: Partnering directly with pts enables rapid identification of thousands of pts willing to share tumors, blood, saliva, and medical records to accelerate research. This approach allows for identification of patients with specific phenotypes, who have been challenging to identify with traditional approaches. Remote acquisition of medical records and saliva/blood/tumor samples is feasible. This clinically annotated dataset is a shared resource for the research community. Table 1Clinical data collection, biospecimen acquisition, and genomic data generation:NumberConsent signed3290 ptsSurvey #1 submitted3290 pts(demographics, diagnosis details, receptor status, clinical experiences)Survey #2 submitted1435 pts(pathology details, sites of metastasis, treatments with start and stop dates)Medical record received1307 ptsSaliva sample received1976 ptsBlood sample received1121 ptsTumor samples received482 tumor samples from 346 ptsDigital image of tumor slide H & E generated482 tumor samplesWES from germline complete310 germline samplesWES from tumor sample complete341 tumor samplesRNA-seq from tumor sample complete229 tumor samplesULP-WGS from cfDNA complete947 blood samplesWES from circulating tumor DNA complete122 blood samples Citation Format: Nikhil Wagle, Corrie Painter, Elana Anastasio, Michael Dunphy, Mary McGillicuddy, Esha Jain, Tania G Hernandez, Sara Balch, Beena Thomas, Dewey Kim, Alyssa L. Damon, Shahrayz Shah, Brett N. Tomson, Rachel Stoddard, Colleen Nguyen, Jorge Buendia-Buendia, Ofir Cohen, Jorge Gomez Tejeda Zanudo, Netsanet Tsegai, Lauren Sterlin, Ulcha Fergie Ulysse, Kathryn Sine, Oyin Alao, Jacqueline Lucia, Eric S. Lander, Todd R. Golub. The metastatic breast cancer project: Generating the clinical and genomic landscape of metastatic breast cancer through patient-partnered research [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD8-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. OT-18-01-OT-18-01
    Abstract: The Metastatic Breast Cancer Project (MBCproject) is an ongoing research study that directly engages patients (pts) through social media and advocacy groups, and empowers them to share their samples, clinical information, and experiences. The goal is to create a publicly available dataset of linked genomic, clinical, and pt-reported data to enable research. In collaboration with pts, advocates, and advocacy groups, a website (MBCproject.org) was developed that allows pts with metastatic breast cancer (MBC) anywhere in the US or Canada to register. From 10/20/15-3/31/20, 5708 women and men with MBC registered for the MBCproject. Registered pts are sent an online consent form that asks for permission to obtain and analyze their medical records and samples. Consented pts are sent a saliva and/or blood kit and asked to mail back a saliva sample, which is used to extract germline DNA, and/or a blood sample, which is used to extract germline DNA and cell free DNA (cfDNA). We contact participants’ medical providers to obtain medical records and a portion of their stored tumor biopsies. 3245 pts receiving care at over 1700 different institutions have consented to share medical records and tumor/saliva/blood samples and to have genomic analysis performed. Whole exome sequencing (WES) is performed on tumor DNA, germline DNA, and cfDNA; transcriptome sequencing (RNA-seq) is performed on tumor RNA. Medical records and pt-reported data are abstracted to create a detailed clinical record for each pt. Table 1 highlights clinical data collection, biospecimen acquisition, and genomic data generation to date. Examples of clinicogenomic analyses are shown in Table 2. De-identified linked genomic, clinical, and pt-reported data is shared regularly via public and semi-public databases (mbcproject.org, cBioPortal, dbGaP, NCI Genomic Data Commons). To date, this data has been cited in over 20 published journal articles. Study updates are shared with participants regularly. The MBCproject continues to enroll new patients, generate additional data, and perform integrated clinical and genomic analyses with the goal of building a dataset that is representative of patients with MBC. We have partnered with over 30 non-profit breast cancer advocacy groups. We also have several community engagement efforts underway to more directly reach patients in underrepresented communities, including partnerships with faith-based organizations and colleges/universities, as well as targeted engagement with the African American community. In addition, in partnership with Latinx patients, advocates, and researchers, the project has been translated into Spanish and is expected to launch in late 2020. Partnering directly with pts rapidly enables thousands of pts to remotely share tumors, blood, saliva, and medical records to accelerate research. The resulting publicly shared clinically annotated database is a resource that allows researchers to identify patients with specific phenotypes, who have often been challenging to identify with traditional approaches. Clinical data collection, biospecimen acquisition, and genomic data generation:NumberConsent signed (US & CA)3245 ptsSurvey #1 submitted(demographics, diagnosis details, receptor status, clinical experiences)3245 ptsSurvey #2 submitted(pathology details, sites of metastasis, treatments with start and stop dates)1638 ptsMedical record received1352 ptsSaliva sample received2004 ptsBlood sample received1121 ptsTumor samples received585 tumor samples from 424 ptsDigital image of tumor slide H & E generated585 tumor samplesWES from germline complete458 germline samplesWES from tumor (primary and metastatic) samples complete343 tumor samplesRNA-seq from tumor (primary and metastatic) samples complete228 tumor samplesULP-WGS from cfDNA (taken in metastatic setting) complete993 blood samplesWES from circulating tumor DNA (taken in metastatic setting) complete143 blood samples CohortConsented (US & CA)Tumor WES completeTumor RNA-seq completePts diagnosed & lt; 40 yrs of age107312071De novo MBC112712183Late recurrence ( & gt;5 years after dx)8307752Long term survivors (MBC & gt; 10yrs)158115Resistance to CDK4/6 inhibitors70914839NED at time of f/u survey4238939Triple Negative Breast Cancer3107531Patients with 2 or more tumor biopsies / cfDNA samples collected by the MBCproject2876138 Citation Format: Nikhil Wagle, Corrie Painter, Elana Anastasio, Michael Dunphy, Mary McGillicuddy, Esha Jain, Brett Tomson, Tania G. Hernandez, Beena Thomas, Dewey Kim, Alyssa L. Damon, Shahrayz Shah, Rafael Ramos, Colleen Nguyen, Lee O'Neil, Sarah Winnicki, Sara Balch, Rachel Stoddard, Taylor Cusher, Parker Chastain, Jorge Gomez Tejeda Zanudo, Jorge Buendia-Buendia, Ofir Cohen, Netsanet Tsegai, Lauren Sterlin, Ulcha F. Ulysse, Imani Boykin, Kate Sine, Oyin Alao, Jacqueline Lucia, Eric S. Lander, Todd R. Golub. The metastatic breast cancer project: Generating the clinical and genomic landscape of metastatic breast cancer through patient-partnered research [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-18-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5371-5371
    Abstract: The Metastatic Breast Cancer Project (MBCproject) is a research study that directly engages patients (pts) through social media and advocacy groups, and empowers them to share samples, clinical data, and experiences. The goal is to create a publicly available database of genomic, molecular, clinical, and patient-reported data to enable research. Working with pts and advocates, a website (MBCproject.org) was developed that allows pts with metastatic breast cancer (MBC) to register. Registered pts are sent an online consent form that asks for permission to obtain and analyze their medical records and samples. Once enrolled, pts are sent a saliva kit and asked to mail back a saliva sample, which is used to extract germline DNA. We contact participants' medical providers and obtain medical records and a portion of their stored tumor biopsies. Pts may be asked to mail in a blood sample, which is used to extract cell free DNA (cfDNA). Whole-exome sequencing (WES) is performed on tumor DNA, germline DNA, and cfNDA; transcriptome sequencing is performed on tumor RNA. Clinically annotated genomic data are used to study specific pt cohorts (including outliers) and to identify mechanisms of response and resistance to therapies. All de-identified data are shared via public databases. Study updates are shared with participants regularly. From 10/2015-11/2017, 4237 MBC pts registered, representing over 1,000 institutions. 95% answered the 16-question survey about their cancer, treatments, and demographic information. 2471 (58%) completed the consent form. 2,136 saliva kits were mailed to pts and 1,523 saliva samples were sent in (71%). 408 blood kits were mailed to pts and 175 blood samples have been received for cfDNA analysis. To date, we have obtained medical records from 311 pts and 190 tumors from 127 pts. In 10/2017, all data generated so far were publicly released on cbioportal.org, including WES for 103 tumors from 78 pts linked to clinical data including pathology (22 elements), medical record abstraction including all treatments and timelines/durations (67 elements), and patient-reported data (11 elements). 81% of biopsies included in this release were from the breast and 19% from metastatic sites. 75% were obtained prior to any therapy, 24% following therapy. New data will be released 4/2018 and every six months thereafter, as they are generated. Additional patient-reported data, including treatments, side effects, quality of life, family history, pregnancies, and sites of metastasis, will also be collected and shared. In summary, a patient-driven approach enabled rapid identification of thousands of MBC pts willing to share samples and clinical data. Remote acquisition of medical records, saliva, blood, and tumor tissue for pts across the U.S. is feasible. This shared clinico-genomic database should enable research in MBC and may serve as a model for patient-driven research in other cancers. Citation Format: Nikhil Wagle, Corrie Painter, Elana Anastasio, Michael Dunphy, Mary McGillicuddy, Rachel Stoddard, Esha Jain, Dewey Kim, Simona Di Lascio, Brett N. Tompson, Sara Balch, Beena Thomas, Priti Kumari, Shawn Johnson, Jamie Holloway, Ofir Cohen, Erik H. Knelson, Katie Larkin, Sam Pollock, Alicia Wong, Samira Bahl, Simone Maiwald, Andrew Zimmer, Esme O. Baker, Jen Hendry Lapan, Scott Sutherland, Scott Sassone, Viktor Adalsteinsson, Eric S. Lander, Todd R. Golub. The Metastatic Breast Cancer Project: Partnering with patients to accelerate progress in cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5371.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. LB-265-LB-265
    Abstract: Human breast cancers can be broadly classified based on their molecular and gene expression profiles into luminal and basal-like tumors. These tumor subtypes express markers corresponding to the two major differentiation states of epithelial cells in the breast: luminal cells that line the breast ducts and the outer myoepithelial/basal cells that provide contractile functions. Women with inherited mutations in the BRCA1 gene have increased breast cancer risk and also exhibit a specific predisposition to the development of aggressive basal-like breast cancers. Accumulating evidence suggests that BRCA1 has a role in breast epithelial differentiation and we wanted to further understand how this could contribute to the formation of basal-like tumors. Microarray, flow cytometry and immunohistochemical analysis of breast epithelial cells from disease-free women harboring deleterious mutations in BRCA1 (BRCA1 mut/+) compared to those from BRCA1 +/+ reduction mammoplasties showed an increase in markers of basal differentiation and a decrease in markers of luminal differentiation. We also created breast cancers from single cell suspensions of BRCA1 mut/+ and BRCA1 +/+ epithelial cells that had been transformed with identical oncogenes and injected into humanized mammary fat pads. Tumors derived from BRCA1 mut/+ cells had increased basal differentiation relative to cells obtained from BRCA1 +/+ patients, indicating that the perturbed differentiation evident prior to neoplastic transformation was mirrored in the tumors. Pathway analysis of the microarray data comparing BRCA1 mut/+ and BRCA1 +/+ cells from disease-free tissue indicated that signaling components relating to the transcriptional repressor Slug were overexpressed in BRCA1 mut/+ tissues. We confirmed that Slug protein levels were elevated in BRCA1 mut/+ tissues and in human tumors from BRCA1 mutation carriers. RNAi-mediated downregulation of slug in primary breast epithelial cells and cell lines derived from BRCA1 mut/+ tissue as well as breast cancer cell lines known to harbor BRCA1 mutations, led to a decrease in markers of basal differentiation, indicating that elevated Slug protein levels seen in BRCA1-associated tissues and tumors are contributing to the basal phenotype. Furthermore, RNAi-mediated knockdown of BRCA1 led to an increase in Slug protein expression and breast cancer cell lines harboring BRCA1 mutations showed an increase in Slug protein stability, indicating that loss of BRCA1 protein by mutation contributes to elevated Slug protein levels. These results reveal an important mechanism by which BRCA1 can regulate breast epithelial differentiation and may explain how, in addition to affecting incidence rates, the genetic background of patients could impact tumor phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-265.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...