title: Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer.
abstract: Gastric cancer and esophageal cancer are the second and sixth leading causes of cancer-related death worldwide. Multiple genomic alterations underlying gastric cancer and esophageal squamous cell carcinoma (ESCC) have been identified, but the full spectrum of genomic structural variations and mutations have yet to be uncovered. Here, we report the results of whole-genome sequencing of 30 samples comprising tumor and blood from 15 patients, four of whom presented with ESCC, seven with gastric cardia adenocarcinoma (GCA), and four with gastric noncardia adenocarcinoma. Analyses revealed that an A>C mutation was common in GCA, and in addition to the preferential nucleotide sequence of A located 5 prime to the mutation as noted in previous studies, we found enrichment of T in the 5 prime base. The A>C mutations in GCA suggested that oxidation of guanine may be a potential mechanism underlying cancer mutagenesis. Furthermore, we identified genes with mutations in gastric cancer and ESCC, including well-known cancer genes, TP53, JAK3, BRCA2, FGF2, FBXW7, MSH3, PTCH, NF1, ERBB2, and CHEK2, and potentially novel cancer-associated genes, KISS1R, AMH, MNX1, WNK2, and PRKRIR Finally, we identified recurrent chromosome alterations in at least 30% of tumors in genes, including MACROD2, FHIT, and PARK2 that were often intragenic deletions. These structural alterations were validated using the The Cancer Genome Atlas dataset. Our studies provide new insights into understanding the genomic landscape, genome instability, and mutation profile underlying gastric cancer and ESCC development. Cancer Res; 76(7); 1714-23. ©2016 AACR.
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Nan
authors: N
authors: Hu
authors: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Mitsutaka
authors: M
authors: Kadota
authors: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Huaitian
authors: H
authors: Liu
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Christian C
authors: CC
authors: Abnet
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Hua
authors: H
authors: Su
authors: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Hailong
authors: H
authors: Wu
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Neal D
authors: ND
authors: Freedman
authors: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Howard H
authors: HH
authors: Yang
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Chaoyu
authors: C
authors: Wang
authors: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Chunhua
authors: C
authors: Yan
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Lemin
authors: L
authors: Wang
authors: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Sheryl
authors: S
authors: Gere
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. Cancer Genomics Research Laboratory, Leidos, Gaithersburg, Maryland.
authors: Amy
authors: A
authors: Hutchinson
authors: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Guohong
authors: G
authors: Song
authors: Shanxi Cancer Hospital, Taiyuan, Shanxi, PR China.
authors: Yuan
authors: Y
authors: Wang
authors: Shanxi Cancer Hospital, Taiyuan, Shanxi, PR China.
authors: Ti
authors: T
authors: Ding
authors: Cancer Institute, Chinese Academy of Medical Sciences, Beijing, PR China.
authors: You-Lin
authors: YL
authors: Qiao
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Jill
authors: J
authors: Koshiol
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Sanford M
authors: SM
authors: Dawsey
authors: Information Management Services, Inc., Silver Spring, Maryland.
authors: Carol
authors: C
authors: Giffen
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors: Alisa M
authors: AM
authors: Goldstein
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. ptaylor@mail.nih.gov leemax@mail.nih.gov.
authors: Philip R
authors: PR
authors: Taylor
authors: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. ptaylor@mail.nih.gov leemax@mail.nih.gov.
authors: Maxwell P
authors: MP
authors: Lee
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods*; D006801:Humans; D008297:Male; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology