In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5027-5027
Abstract:
Although the progress in moving from a one-size-fits-all cytotoxic approach to personalized molecular medicine, majority of the patients with cancer receive chemotherapy with cytotoxic anticancer drugs. Exome sequencing of 409 cancer related genes was conducted using 59 DNAs extracted from human tumor xenografts implanted into nude mice, of which sensitivity to nine cytotoxic anticancer drugs (5-fluorouracil (5FU), Nimustine (ACNU), adriamycin (ADR), cyclophosphamide (CPM), cisplatin (DDP), mitomycin C (MMC), methotrexate (MTX), vincristine (VCR), and vinblastine (VLB)) had been examined. We investigated the relationship between the sensitivities of the xenografts to the nine anticancer drugs and single nucleotide variants (SNVs) by classifying them into three groups according to the allele frequency (≤10%, 10-90%, ≥90%). We further carried out replication study using additional set of 20 xenografts. We also estimated the correlation between the expression levels of the 409 genes and sensitivities to the nine drugs in the above xenografts. In the screening stage using 59 xenografts, three SNVs, which were associated with sensitivity to VCR or MMC, showed P & lt; 0.001. We further carried out a replication study of 596 SNVs showing P & lt; 0.05 in the screening stage using independent samples of 20 xenografts. A combined result of the screening and replication studies suggested possible associations of 35 SNVs with sensitivities to the nine anticancer drugs (Pcombined = 0.0011 - 0.035). A total of 35 SNVs showed possible association with sensitivity to at least one of the nine drugs. Of the 35 SNVs, SNV-1 and SNV-2 in a tumor suppressor gene and a oncogene were commonly associated with sensitivity to two or four anticancer drugs, respectively. These findings provide new insights into precision anticancer therapy for the patients with cancer. Citation Format: Chihiro Udagawa, Yasushi Sasaki, Hiroshi Suemizu, Yasuyuki Ohnishi, Hiroshi Ohnishi, Takashi Tokino, Hitoshi Zembutsu. Exome sequencing of cancer-related genes to identify genetic markers for sensitivity to cytotoxic anticancer drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5027. doi:10.1158/1538-7445.AM2017-5027
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-5027
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
