GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
Filter
  • American Society of Clinical Oncology (ASCO)  (19)
  • 1
    Online Resource
    Online Resource
    Development and validation of a genomic signature to identify colorectal cancer patients with microsatellite instability.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 4_suppl ( 2012-02-01), p. 466-466
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 466-466
    Abstract: 466 Background: Microsatellite Instability (MSI-H) occurs in 10-20% of colon tumors and has been attributed predominantly to gene silencing of DNA mismatch repairs (MMR) genes by mutation or methylation, including MSH2, PMS2 and in particular MLH1. Methods: MSI status for 276 primary stage II and III colorectal tumors have been determined (n=29 MSI-H, n=247 MSS and MSI-L) by immunohistochemically staining of MLH1 and PMS2 (for 90 patients) or by PRC amplification of six microsatellite DNA regions from paired normal and tumor tissues (for 186 patients). Full genome gene expression data for the same 276 tumors was available and used to identify genes that correlate with MSI-H status. All samples had full clinical information including 5-year follow-up and ColoPrint results (as described in Salazar et al. JCO 2011). Results: Most MSI-H patients were classified as ColoPrint low risk (26 of 29 patients; 90%) however this is only as subgroup of the 195 patients identified by ColoPrint as low risk. While ColoPrint had great prognostic power in this dataset (HR 2.37, p=0.0006), it does not identify MSI-H patients with high specificity. We therefore developed a MSI-gene signature of 64 genes using a 10-fold cross validation procedure to complement ColoPrint. The MSI-signature identifies MSI-H patients with high sensitivity (93.1% (27/29)) and high specificity (87.9% (217/247)) and an overall accuracy of 88.4% (244/276). The MSI-signature has prognostic power in the subset of stage II patients (n=215) with HR = 2.38 (95% CI 1.15-4.93, p=0.06. However, in multivariate analysis of MSI status and all clinical factors, ColoPrint was the only significant prognostic factor (HR 3.2; p=0.0014). The MSI-signature is currently validated in an independent patients set of 132 stage II patients (31 MSI-H, 101 MSS). Conclusions: The diagnostic MSI signature identifies patients with MSI-H status with high accuracy. In combination with the prognostic power of ColoPrint, the identification of MSI-H patients might add additional information for treatment of stage II patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.4_suppl.466
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Comparison of three molecular methods to detect mutations in KRAS , NRAS , BRAF and PIK3CA in metastatic colorectal cancer (mCRC).
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 3559-3559
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 3559-3559
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.3559
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Prospective study of germline and somatic alterations for early onset lung cancer patients (EOLUNG MASTER protocol).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. TPS9122-TPS9122
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. TPS9122-TPS9122
    Abstract: TPS9122 Background: Lung cancer (LC) is a rare disease among young adults. Polymorphisms in genes involved in carcinogenic metabolism of tobacco and/or xenobiotic metabolism have been identified in those patients. The growing use of next generation sequencing (NGS) unravelled germline mutations in genes associated with hereditary cancer in patients with LC. However, germline DNA mutations have not been systematically studied in young adults with LC. Early onset LC patients are likely to harbor actionable somatic mutations. Broad hybrid NGS can identify actionable genomic alterations in LC patients deemed driver negative by routine molecular analysis. Trial Design: This is a multicentre, prospective, single-cohort study to determine whether young patients with LC harbor germline mutations and to evaluate the impact of NGS using Foundation One platform on the therapeutic options and overall survival for this specific patient population. Major inclusion criteria: 1) patients already or newly diagnosed of non-small cell lung cancer at any stage at age 〈 51; 2) to have sufficient tumor sample to perform standard molecular diagnosis ( EGFR/ALK/ROS1/BRAF); 3) to provide written informed consent for the study. Methods: After signing the informed consent form, family history of cancer and smoking history will be collected and a peripheral blood sample will be obtained. Germline targeted sequencing will be carried out in our centre using a customized hereditary cancer panel (I2HCP) of 136 genes designed to cover the coding exons and intron-exon boundaries of genes associated with moderate or high risk of hereditary cancer. Patients with clinical criteria for hereditary cancer or harboring pathogenic or probably pathogenic germline alteration will be referred to the genetic counselling unit. Patients will follow the usual clinical pathway for biomarker analysis and in case of remaining tumour material it will be used for conducting comprehensive genomic profiling through Foundation One platform. When tumour material available will not be sufficient to perform NGS, a tumour re-biopsy will be considered. Enrolment begun on June 2018 and, to date, a total of 41 patients have been included in the study.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.TPS9122
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Association of colorectal cancer intrinsic subtypes with prognosis, chemotherapy response, deficient mismatch repair, and epithelial to mesenchymal transition (EMT).
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 4_suppl ( 2013-02-01), p. 333-333
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 333-333
    Abstract: 333 Background: Unbiased genome-wide analyses of gene expression patterns have been successfully used for the molecular classification of breast cancer into subtypes that have clear relevance for prognosis and development of treatment plans. For colorectal cancer (CRC), however, a molecular classification is still missing. Methods: Using gene expression data of 188 stage I-IV colorectal cancer (CRC) patients, a molecular subtype classification was developed. The classifier was validated in 543 stage II and III patients and the subtypes were analyzed for correlation to clinical information, mutations in the kinome, known molecular marker status and chemotherapy response. Results: CRC is a heterogeneous disease that consists of at least three major intrinsic subtypes (A-, B-, C-type). The heterogeneity of the intrinsic subtypes is largely based on three biological hallmarks of the tumor: an epithelial-to-mesenchymal transition, deficiency in mismatch repair genes that result in a high mutation frequency associated with MSI, and cellular proliferation. C-type patients have the worst outcome, a mesenchymal gene expression phenotype, and show no benefit from adjuvant chemotherapy treatment. Patients having A-type or B-type tumors have a better clinical outcome, a more proliferative and epithelial phenotype, and benefit from adjuvant chemotherapy. B-type tumors showed a low overall kinome mutation frequency (1.6%), while both A-type and C-type patients harbor a higher mutation frequency (respectively 4.2 and 6.2%), in agreement with their mismatch repair deficiency. Conclusions: We have developed a diagnostic single sample predictor that allows the classification of CRC tumors of different intrinsic molecular subtypes. These subtypes are potentially clinically relevant, as they differ in their underlying biology and clinical outcome and consequently require different treatment strategies. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.4_suppl.333
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 4 ( 2015-02-01), p. 319-325
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 4 ( 2015-02-01), p. 319-325
    Abstract: The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Methods Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome–associated cancers. Results The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P 〈 .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis. Conclusion CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2014.57.8088
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Tumor Thymidylate Synthase 1494del6 Genotype As a Prognostic Factor in Colorectal Cancer Patients Receiving Fluorouracil-Based Adjuvant Treatment
    American Society of Clinical Oncology (ASCO) ; 2006
    In:  Journal of Clinical Oncology Vol. 24, No. 10 ( 2006-04-01), p. 1603-1611
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 10 ( 2006-04-01), p. 1603-1611
    Abstract: The purpose of this study was to analyze the value of germline and tumor thymidylate synthase (TS) genotyping as a prognostic marker in a series of colorectal cancer patients receiving adjuvant fluorouracil (FU) -based treatment. Patients and Methods One hundred twenty-nine colorectal cancer patients homogeneously treated with FU plus levamisole or leucovorin in the adjuvant setting were included. TS enhancer region, 3R G 〉 C single nucleotide polymorphism (SNP), and TS 1494del6 polymorphisms were assessed in both fresh-frozen normal mucosa and tumor. Mutational analyses of TS and allelic imbalances were studied in all primary tumors and in 18 additional metachronic metastases. TS protein immunostaining was assessed in an expanded series of 214 tumors. Multivariate Cox models were adjusted for stage, differentiation, and location. Results Tumor genotyping (frequency of allelic loss, 26%) showed that the 3R/3R genotype was associated with a better outcome (hazard ratio [HR] = 0.38; 95% CI, 0.16 to 0.93; P = .020 for the recessive model). 3R G 〉 C SNP genotyping did not add prognostic information. Tumor TS 1494del6 allele (frequency of allelic loss, 36%) was protective (for each allele with the deletion, based on an additive model, HR = 0.42; 95% CI, 0.22 to 0.82; P = .0034). Both polymorphisms were in strong linkage disequilibrium (D' = 0.71, P 〈 .001), and the 3R/–6 base pair (bp) haplotype showed a significant overall survival benefit compared with the most prevalent haplotype 2R/+6bp (HR = 0.42; 95% CI, 0.20 to 0.85; P = .017). No TS point mutation was detected in primary tumors or metastases. TS protein immunostaining was not associated with survival or any of the genotypes analyzed. Conclusion Tumor TS 1494del6 genotype may be a prognostic factor in FU-based adjuvant treatment of colorectal cancer patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2005.03.5253
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2006
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Searching for new genes responsible for unexplained hereditary breast and ovarian cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e12516-e12516
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e12516-e12516
    Abstract: e12516 Background: About 10-20% of breast and ovarian cancer patients show family history of the disease. Germline mutations in the BRCA1 and BRCA2 genes are usually found in 20-25% of these cases, while the remaining ones are commonly known as BRCAX. Next generation sequencing (NGS) studies have the promise to expedite the identification of the genetic basis underlying BRCAX cases. Aim: To identify gene mutations associated with BRCAX cases by means of whole exome sequencing. Methods: Five selected BRCAX families with more than three affected individuals across at least three generations, and with an apparent dominant pattern of inheritance of the disease were selected in this study. All type of potential alterations of BRCA1/2and linkage to the corresponding loci were excluded in these families. For sequencing, libraries representing the whole exome of multiple affected individuals were obtained using the SureSelect Human All Exon 50 Mb Kit (Agilent) together with the Paired-End Sample Preparation Kit (Illumina) following manufacturers' protocols. Bioinformatics analysis to identify candidate variants present in each family was performed as previously described (PubMed ID: 21549337). Selected rare variants have been analyzed in a set of 288 controls and are currently being evaluated in 500 additional BRCAX cases. Results: By using the described workflow we have identified 16 candidate genes. They were selected based on the presence of rare missense variants that were not found in our control group, predicted as pathogenic using several algorithms (SIFT, PoplyPhen2, Condel and Mutation Taster). Currently, we are re-sequencing these genes in a set of BRCAX samples and complementarily performing loss-of-heterozigosity studies in tumor samples. Conclusions: Exome sequencing of 20 patients from 5 independent Spanish BRCAX families identified a list of putative new BRCAX genes that are currently in the process of validation. Identification of the genetic causes underlying breast and ovarian cancer in BRCAX families is paramount to perform genetic counseling and individual risk assessment in these patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e12516
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Treatment focused genetic testing (TFGT) for ovarian cancer (OC) patients: The Catalan Institute of Oncology (ICO) network experience.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. e17071-e17071
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e17071-e17071
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.e17071
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Induction of an aggressive phenotype and poor survival in early-stage lung adenocarcinoma and epigenetic inactivation of microRNA-34b/c.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 11056-11056
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 11056-11056
    Abstract: 11056 Background: The microRNA-34b/c (miR-34b/c) is a transcriptional target of TP53 that is frequently mutated in primary lung adenocarcinoma (AC). We investigated the clinical implications of miR-34b/c methylation in early stage lung AC patients and the functional role of miR-34b/c re-expression in lung AC cell lines. Methods: DNA methylation of miR-34b/c promoter was assessed by real-time PCR temperature dissociation in 15 lung AC cell lines and 140 early stage lung AC resected at the Bellvitge Hospital (Barcelona) and at the University of Michigan (Ann Arbor). Patient characteristics: 65% males, 88% smokers, 68.5% stage I and 31.5% stage II. Expression of miR-34b/c was determined by TaqMan RT-PCR. Two lung AC cell lines (NCI-H1838 and SK-LU-1) were transfected with an expression vector containing both miRs and the effects upon cell proliferation, migration and invasion were determined. Results: MiR-34b/c was methylated in 40% of cell lines and in 46% of primary tumors with significant association with higher tumor stage (P=0.033), recurrence (P=0.017) and death (P=0.005). In the training set (n=58), patients with higher levels of miR-34b/c methylation had significantly shorter median DFS (28.5 months) compared to low to medium levels (not reached, log-rank P=0.016). In the test set (n=82), higher levels of miR-34b/c methylation were also associated to shorter median DFS (19 months) compared to patients with low to medium levels (not reached, log-rank P=0.005). MiR-34b/c methylation remained an independent prognostic marker for DFS after adjusting by age, gender and stage. Tumors harboring TP53 mutations and miR-34b/c methylation expressed significantly lower levels of miR-34b/c (P≤0.001). Stable cells expressing miR-34b/c had lower proliferation rate relative to cells transfected with empty vector (P≤0.001). Expressing miR-34b/c in SK-LU-1 cells reduced migration and invasion ability. Conclusions: Epigenetic inactivation of miR-34b/c by DNA methylation is an independent prognostic marker in early stage lung AC. Ectopic expression of miR-34b/c generated a less aggressive phenotype in lung AC cell lines suggesting a potential for therapeutic targeting.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.11056
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Cancer risk and overall survival in APC I1307K carriers.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 1592-1592
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 1592-1592
    Abstract: 1592 Background: The germline variant APC I1307K is one of the most commonly identified pathogenic variants on germline genetic testing panels. The purpose of the Molecular Epidemiology of Colorectal Cancer study was to quantify the risk of colorectal cancer among carriers, characterize the clinical, pathologic, and molecular features of colorectal cancers arising in patients with APC I1307K, and to describe the overall and disease-specific survival of carriers with colorectal cancer. Here, the final results of the Molecular Epidemiology of Colorectal Cancer Study are reported with respect to APC I1307K. Methods: We consented 6,006 incident, pathologically confirmed cases of colorectal adenocarcinoma and 5,023 age, sex, and ethnicity matched controls without colorectal cancer between March 31, 1998 and July 1, 2017 within a geographically defined area of Northern Israel. Comprehensive, in-person epidemiologic interviews were conducted for cases and controls, with uniform histopathologic review, detailed molecular analysis, medical record review and clinical follow-up for up to 21 years. Results: The demographic and clinical features of incident colorectal cancer cases matched the population distribution of colorectal cancer in Israel. APC I1307K was identified in 429 (7.1%) of cases and 201 (4.0%) of controls. The estimated relative risk of colorectal cancer among carriers was 1.89 (95% confidence interval, 1.59 - 2.24), p 〈 0.0001. The prevalence and odds ratios differed by ethnic group. Homozygous carriers were at especially high risk, with an odds ratio of 3.90 (95% confidence interval 1.11–13.71). APC I1307K carriers were significantly less likely to have microsatellite instable tumors (p = 0.04). Overall survival of APC I1307K carriers was not significantly different than survival of non-carriers, after adjustment for age, stage, sex, ethnicity, and microsatellite instability. Conclusions: APC I1307K is an actionable germline mutation that confers meaningful lifetime risk of colorectal cancer in heterozygous and homozygous carriers. APC I1307K is not an independent prognostic factor for overall survival or disease specific survival and is not associated with the MSI phenotype. Cumulative lifetime risk estimates inform genetic counseling and provide data for policies regarding the timing and frequency of screening and other preventive strategies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.1592
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...