title: Colorectal Cancer Genetic Heterogeneity Delineated by Multi-Region Sequencing.
abstract: Intratumor heterogeneity (ITH) leads to an underestimation of the mutational landscape portrayed by a single needle biopsy and consequently affects treatment precision. The extent of colorectal cancer (CRC) genetic ITH is not well understood in Chinese patients. Thus, we conducted deep sequencing by using the OncoGxOne™ Plus panel, targeting 333 cancer-specific genes in multi-region biopsies of primary and liver metastatic tumors from three Chinese CRC patients. We determined that the extent of ITH varied among the three cases. On average, 65% of all the mutations detected were common within individual tumors. KMT2C aberrations and the NCOR1 mutation were the only ubiquitous events. Subsequent phylogenetic analysis showed that the tumors evolved in a branched manner. Comparison of the primary and metastatic tumors revealed that PPP2R1A (E370X), SETD2 (I1608V), SMAD4 (G382T), and AR splicing site mutations may be specific to liver metastatic cancer. These mutations might contribute to the initiation and progression of distant metastasis. Collectively, our analysis identified a substantial level of genetic ITH in CRC, which should be considered for personalized therapeutic strategies.
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China.|Faculty of medical, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China.
authors.forename: You-Wang
authors.initials: YW
authors.lastname: Lu
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China.|Department of Pharmacy, The First People's Hospital of Yunnan Province, Kunming, Yunnan, P.R. China.
authors.forename: Hui-Feng
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Department of Pathology, First People's Hospital of Yunnan Province, Kunming, Yunnan, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.affiliation: Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
authors.forename: Zhen-Rong
authors.initials: ZR
authors.lastname: Xie
authors.affiliation: Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Department of Gastrointestinal and Hernia surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Jie-Shou Li Academician Workstation, Kunming, Yunnan, P.R. China.
authors.forename: Hua-You
authors.initials: HY
authors.lastname: Luo
authors.affiliation: Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Department of Gastrointestinal and Hernia surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Jie-Shou Li Academician Workstation, Kunming, Yunnan, P.R. China.
authors.forename: Yu-Jian
authors.initials: YJ
authors.lastname: Zeng
authors.affiliation: Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Department of Gastrointestinal and Hernia surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Jie-Shou Li Academician Workstation, Kunming, Yunnan, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Faculty of medical, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China.
authors.forename: La-Mei
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China.|Faculty of medical, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Kong
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, P.R. China.|Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Department of Gastrointestinal and Hernia surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Jie-Shou Li Academician Workstation, Kunming, Yunnan, P.R. China.
authors.forename: Kun-Hua
authors.initials: KH
authors.lastname: Wang
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*