Dataset Information

Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma.

ABSTRACT: Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four-stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a 'parallel' evolution of synchronous adenoma-to-carcinoma, rather than a 'stepwise' evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent.

SUBMITTER: Kim TM

PROVIDER: S-EPMC4695021 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma.

Kim Tae-Min TM An Chang Hyeok CH Rhee Je-Keun JK Jung Seung-Hyun SH Lee Sung Hak SH Baek In-Pyo IP Kim Min Sung MS Lee Sug Hyung SH Chung Yeun-Jun YJ

Oncotarget 20150901 29

Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four-stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired ca ...[more]

PMID: 26336987

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Dataset Information

Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma.

Publications

Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma.

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