Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

TY - JOUR

T1 - Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

AU - Du, Peina

AU - Huang, Peide

AU - Huang, Xuanlin

AU - Li, Xiangchun

AU - Feng, Zhimin

AU - Li, Fengyu

AU - Liang, Shaoguang

AU - Song, Yongmei

AU - Stenvang, Jan

AU - Brünner, Nils

AU - Yang, Huanming

AU - Ou, Yunwei

AU - Gao, Qiang

AU - Li, Lin

PY - 2017/12

Y1 - 2017/12

N2 - Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC. Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more CNAs and marked for worse prognosis compared with subtype2. Moreover, database annotation suggested that two significantly differential CNA genes (PIK3CA and FBXW7) between subtype3 and subtype2 may serve as therapeutic drug targets. This study has extended our knowledge of the genetic basis of ESCC and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients.

AB - Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC. Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more CNAs and marked for worse prognosis compared with subtype2. Moreover, database annotation suggested that two significantly differential CNA genes (PIK3CA and FBXW7) between subtype3 and subtype2 may serve as therapeutic drug targets. This study has extended our knowledge of the genetic basis of ESCC and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients.

U2 - 10.1038/s41598-017-14909-5

DO - 10.1038/s41598-017-14909-5

M3 - Journal article

C2 - 29127303

AN - SCOPUS:85033573140

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

M1 - 15324

ER -