Paper

Forward-reverse mutation cycles between stages of cancer development

Ho, Timothy Y C, Long, Xi, Xue, Hong, Chan, Cheuk-Hin, Xu, Lin, Yang, Jianfeng, Dan-Hua, Zhang, Li, Yi, Zhou, Xuqing, En-Xiang, Zhou, Wu, Zhenggang, Kumar, Yogesh, Yin, Rong, Iram Shazia, Wai-Sang Poon, Ding, Xiaofan, International Cancer Genome Consortium, Chen, Lei, Lee, Peggy, Hu, Taobo, Siu-Kin Ng, Hong-Yang, Wang, Jin-Fei, Chen, Wai-Kin Mat, Shui-Ying Tsang, Shen-Jia, Duan, Gilberto Ka-Kit Leung, Kwong, Ava

2017

Overview

Earlier, prominent occurrences of interstitial loss-of-heterozygosities (LOHs) were found in different cancers as a type of single-nucleotide-variations (SNVs), at rates far exceeding those of the commonly investigated gain-of-heterozygosities (GOHs) type of SNVs. Herein, such co-occurrences of LOHs and GOHs were confirmed in 102 cases of four cancer types analyzed with three different next-generation sequencing platforms, comparing non-tumor, paratumor, and tumor tissues with white-blood-cell controls; and in 246 pan-cancer cases of whole-genome tumor-control pairs. Unexpectedly, large numbers of SNVs enriched with CG>TG GOHs and copy-number-variations (CNVs) proximal to these GOHs were detected in the non-tumor tissues, which were extensively reversed in paratumors showing prominent TG>CG LOHs with proximal CNVs, and less so in tumors to form forward-reverse mutation cycles. Lineage effects in the reversions, likely resulting from directional selection, supported a sequential rather than parallel mode of evolution as described in a 'Stage Specific Populations' model of cancer development.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Cancer / Cancer Biology / Genomes / Mutation / Next-generation sequencing / Tumors