571P - Correlation between DNA copy number and clinicopathological features: Biomarker search using genome-wide analysis of DNA copy number alterations in...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Translational Research
Presenter Toshiaki Ishikawa
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors T. Ishikawa1, H. Uetake2, K. Murotani3, T. Kobunai4, M. Ishiguro2, S. Matsui5, K. Sugihara1
  • 1Surgical Oncology, Tokyo Medical and Dental University, Graduate School, 113-8519 - Tokyo/JP
  • 2Translational Oncology, Tokyo Medical and Dental University, Graduate School, 113-8519 - Tokyo/JP
  • 3Center For Advanced Medicine And Clinical Research, Nagoya University Graduate School of Medicine, Nagoya/JP
  • 4Laboratory For Oncology Medication Management And Development, Taiho Pharmaceutical Co., Ltd., Tokyo/JP
  • 5Biostatistics, Nagoya University Graduate School of Medicine, Nagoya/JP

Abstract

Aim

The ACTS-CC trial is a phase III designed to validate the noninferiority of S-1 to UFT/leucovorin as adjuvant chemotherapy for stage III colon cancer. As an additional study, a genome-wide analysis of DNA copy number alterations was performed prospectively to identify predictive and/or prognotic biomarkers. DNA copy number alteration profiles of stage III colon cancer was previously reported (AACR2013 adstr#4688). In the present study, we investigated the correlations between DNA copy number and clinicopathological features to extract the characteristics of colon cancer.

Methods

From 795 of 1535 patients enrolled between April 2009 and January 2010, formalin-fixed paraffin-embedded samples of resected tumors were obtained under informed consent. Genomic DNA was extracted from 777 sepecimens using manual macro dissections. After quality assessments using arbitrary PCR and microfluidic analysis, somatic copy-number alterations in tumor were analyzed by high-density SNPs arrays (Human 250K StyI array, Affymetrix, Santa Clara, CA, USA). To detect copy number alterations, the scanned image CEL files were imported into Partek Genomics Suited v6.6 (Partek Inc., . Louis, MO, USA). The associations of genome-wide DNA copy number changes and clinicopathological features of colon cancer were investigated.

Results

Genome-wide DNA copy number alteration profiles of 161 samples were obtained by GeneChip. In the profiles, we observed frequent DNA copy number gains at chromosome 7, 8q and 13, and losses at 4, 5q, 17p and 18q. Specific chromosomal aberrations were significantly related to the clinicopathological features; the tumor location significantly correlated with genomic segments in 7p and 20p, the depth of the tumor with genomic segments in 4q, 8p, chromosome 15 and chromosome 18, and the histological type of the tumor with genomic segments in chromosome 18. Age and gender had no correlation with DNA copy number alterations.

Conclusions

The location, depth, and histological type of the tumor correlated with DNA copy number alteration. Our findings will facilitate understanding the characteristics of colon cancer. Further investigations may contribute to the exploration of valid biomarkers.

Disclosure

T. Ishikawa: has received research funding from Taiho; honoraria from TaihoPharmaceutical Co., Ltd., Merck Serono Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Takeda Pharmaceutical Co., Ltd.; H. Uetake: has received consulting fees, research funding, and honoraria from Taiho, Chugai, Takeda, Bristol-Myers Squibb, and Merck Serono; K. Murotani: has received research funding from Taiho; T. Kobunai: has been employed by Taiho; M. Ishiguro: has received consulting fees from Taiho, Bristol-Myers, and Merck Serono; honoraria from Taiho, Chugai, Yakult Honsha Co., Ltd.; S. Matsui: has received research funding from Taiho; K. Sugihara: has received consultant fees, research funding and honoraria from Taiho, Chugai, Takeda, Yakult Honsha, Daiichi Sankyo Co., Ltd., Bristol-myers, Merck Serono, and Pfizer Co., Ltd.