Distribution features of genomic amplifications in microsatellite stable Chinese colorectal cancer.

Abstract

e15509 Background: Genomic amplification is key mutational events in microsatellite stable (MSS) colorectal cancer (CRC). A distinctive amplification region of CRC is Chr20q. It was revealed by several investigations the most recurrent amplified band in CRC and often co-exist with Chr8q. However, there is very little data to describe the characteristics of chromosome co-exist amplifications in CRC. We did an exploratory analysis in this issue in a large size of Chinese CRC. Methods: A total of 1977 CRC with detected genomic amplifications were included in this analysis. Calling of single nucleotide variants (SNV), copy number variants (CNV), insertion/deletions (indels), fusions were performed using a wide panel next-generation sequencing (NGS) testing. Amplifications were stratified as high-level, moderate-level and low-level according to the number of copies (cut-off: 20, 8 copies). Results: Nine chromosome arm were detected amplified in more than 10% cases in this cohort. Chr20q (65.9%), Chr13q (57.1%) and Chr8q (34.3%) were the most frequent. Chr17q and Chr12q had more high-level amplifications than other chromosome arms with ratio of 54.9% and 33.7%, respectively. In contrast, Chr20q and ChrX substantially had low-level amplifications. 36.2% (715/1977) cases had amplifications on more than two chromosome arms (median 2, range 2-7). In patients (92%) with 2-4 co-current amplified chromosome arms, the most frequent co-amplified patterns were Chr20q-Chr13q (20%) and Chr20q-Chr8q (15%). Most patients among this subgroup had more than three amplified genes in Chr20q while only one amplified gene in Chr8q. In patients (8%) with 5-7 co-current amplified chromosome arms, the most frequent amplified regions were Chr20q, Chr8q and Chr7q, and more than 60% cases harbored Chr20q-Chr8q. Interestingly, these patients mainly had multiple amplified genes in Chr8q and only one amplified gene in Chr20q, in the contrary to the patients with 2-4 co-current amplified chromosome arms. In addition, high-level focal amplifications in Chr17q and Chr12q participated equally to the amplifications with other chromosome arms. Conclusions: Our analysis results suggested the heterogeneity of Chr20q co-amplifications patterns in CRC. Amplifications in Chr20q and Chr8q may play distinct critical roles in the tumorigenesis of CRC. High-level amplifications were, on the other hand, independent of their driven process.