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  • American Association for Cancer Research (AACR)  (2)
  • 1
    Online Resource
    Online Resource
    Abstract 4917: Identification of genetic heterogeneity by whole exome sequencing using cell free DNA from blood samples
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4917-4917
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4917-4917
    Abstract: Objectives: Circulating cell-free DNA (cfDNA) is expected to be useful for diagnosis of genetic alterations in cancer. However, it has been still difficult to comprehensively analyze somatic mutations using cfDNA, because of the low quantity in blood. We examined the feasibility of whole exome sequencing using cfDNA and assessed the ratio of mutation reads in cfDNA for somatic mutations comparing with the corresponding tumor DNA in ovarian cancer specimens. In addition, we assessed whether cell free DNA might reflect the tumor heterogeneity in ovarian cancer. Methods: The pair of fresh frozen tumor samples and blood samples was obtained from two cases of ovarian serous adenocarcinoma under informed consent and approval of institutional review board. The tumor DNA and cfDNA were extracted from the specimens and whole-exome sequencing was performed using 1ug of the tumor DNA or 25ng of cfDNA. The list of the mutated genes was compared between cell free DNA and the corresponding tumor DNA. Validation of the mutations and calculation of the tumor content ratio in cfDNA was assessed using target sequencing. Result: We successfully detected the somatic mutations from cfDNA. The somatic mutations detected in cfDNA covered from 21% (49/233) to 55% (141/258) of the mutations detected in the corresponding tumor DNA. TP53 was included in the mutated genes, and the base substitution (chr17:7578257 C & gt;A) was identified in 5 of 121 reads (4%) in cfDNA. We validated the tumor content ratio of cfDNA is 8% by target sequencing. One of the two cases showed the correlation between the mutant allele frequency in the tumor DNA and the detection ratio of the mutations in cfDNA (p = 0.004, logistic regression analysis). However, the correlation was not observed in another case (p = 0.3923, logistic regression analysis). Of note, we detected various types of mutations in cfDNA alone. One of such genes is RAPGEF2. The base substitution (ch4:160253031 C & gt;T) was detected only in cfDNA (11/53, 21%), but not in tumor DNA (0/120, 0%). Conclusion: Our data suggest that whole exome sequencing of cfDNA is feasible. The mutations detected only in cfDNA might reflect the tumor heterogeneity, and cfDNA might provide us novel biomarkers for diagnosis of recurrence and/or metastasis. Further study is warranted to elucidate the method to utilize the genetic information from cfDNA. Note: This abstract was not presented at the meeting. Citation Format: Kayo Asada, Katsutoshi Oda, Kengo Gotoh, Reiko Kurikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Yuji Ikeda, Yuriko Uehara, Kenbun Sone, Osamu Hiraike-Wada, Kei Kawana, Tetsu Yano, Yutaka Osuga, Tomoyuki Fujii, Hiroyuki Aburatani. Identification of genetic heterogeneity by whole exome sequencing using cell free DNA from blood samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4917. doi:10.1158/1538-7445.AM2015-4917
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-4917
    RVK:
    XA 36000
    RVK:
    XA 10000
    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
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  • 2
    Online Resource
    Online Resource
    Abstract 1356: Frequent H3F3A K27M mutations in thalamic gliomas from young adult patients
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 1356-1356
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 1356-1356
    Abstract: Introduction. Mutations in the H3F3A gene, which encodes histone H3.3, were recently reported in cases of pediatric glioblastoma. H3F3A K27M mutations occur in gliomas that arise at midline locations, including the pons, thalamus, and spine; moreover, this particular mutation is found mainly in tumors in children and adolescents. In this study, we aimed to determine the association between H3F3A mutations and adult thalamic glioma. Methods. Genomic H3F3A was sequenced from 20 separate thalamic gliomas. Of the 20 tumors, 18 were high-grade thalamic gliomas, and of these 18, 11 were from patients under 50 years of age (median age, 38 years; range, 17 - 46), and seven were from patients more than 50 years of age. Additionally, for 14 of the 20 gliomas, 639 genes_including cancer-related genes and chromatin-modifier genes_were sequenced, and the Infinium HumanMethylation450K BeadChip was used to examine DNA methylation across the genome. Results. The H3F3A K27M mutation was present in 10 of (91%) of the 11 younger patients, and absent from all seven older patients. Additionally, H3F3A K27M was not detected in the two diffuse astrocytomas. By additional sequencing, recurrent mutations were identified in TP53, ATRX, NF1, and EGFR. In addition, a KDM6A mutation was found in one case of diffuse astrocytoma and a CREBBP mutation was identified in one case of glioblastoma with the H3F3A K27M mutation. Gliomas with H3F3A K27M from pediatric or young-adult patients had similar, characteristic DNA methylation profiles. In contrast, thalamic gliomas with wild-type H3F3A had DNA methylation profiles similar to those of hemispheric glioblastomas. Conclusion. We found that high-grade thalamic gliomas from young adults, like those from children and adolescents, frequently have the H3F3A K27M mutation. Citation Format: Akitake Mukasa, Koki Aihara, Kengo Gotoh, Kuniaki Saito, Genta Nagae, Shingo Tsuji, Kenji Tatuno, Shogo Yamamoto, Shunsaku Takayanagi, Yoshitaka Narita, Soichiro Shibui, Hiroyuki Aburatani, Nobuhito Saito. Frequent H3F3A K27M mutations in thalamic gliomas from young adult patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1356. doi:10.1158/1538-7445.AM2014-1356
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2014-1356
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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    Online Resource
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