Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

被引：73

作者：

Hu, Nan ^{[1
]}

Kadota, Mitsutaka ^{[2
]}

Liu, Huaitian ^{[2
]}

Abnet, Christian C. ^{[1
]}

Su, Hua ^{[1
]}

Wu, Hailong ^{[2
]}

Freedman, Neal D. ^{[1
]}

Yang, Howard H. ^{[2
]}

Wang, Chaoyu ^{[1
]}

Yan, Chunhua ^{[2
]}

Wang, Lemin ^{[1
]}

Gere, Sheryl ^{[2
]}

Hutchinson, Amy ^{[1
,3
]}

Song, Guohong ^{[2
]}

Wang, Yuan ^{[4
]}

Ding, Ti ^{[4
]}

Qiao, You-Lin ^{[5
]}

Koshiol, Jill ^{[1
]}

Dawsey, Sanford M. ^{[1
]}

Giffen, Carol ^{[6
]}

Goldstein, Alisa M. ^{[1
]}

Taylor, Philip R. ^{[1
]}

Lee, Maxwell P. ^{[2
]}

机构：

[1] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[2] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[3] Leidos, Canc Genom Res Lab, Gaithersburg, MD USA

[4] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China

[5] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China

[6] Informat Management Serv Inc, Silver Spring, MD USA

来源：

CANCER RESEARCH | 2016年 / 76卷 / 07期

关键词：

MUTATIONAL SIGNATURES; ADENOCARCINOMA; FUSION; GENES; EXOME; IDENTIFICATION; POPULATION; RISK;

D O I：

10.1158/0008-5472.CAN-15-0338

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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>Cmutation 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.

引用

页码：1714 / 1723

页数：10

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