Whole genome sequencing analysis identifies recurrent structural alterations in esophageal squamous cell carcinoma
Whole genome sequencing analysis identifies recurrent structural alterations in esophageal squamous cell carcinoma
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DOI：
10.7717/peerj.9294
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发表时间：
2020-06-26
期刊：
影响因子：
2.7
通讯作者：
Fujita, Masashi
中科院分区：
文献类型：
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作者：
Dutta, Munmee;Nakagawa, Hidewaki;Fujita, Masashi
食管鳞状细胞癌（ESCC）是包括日本在内的亚洲地区食管癌的主要类型。之前的一项研究通过外显子组测序报告了日本食管鳞癌的突变情况。然而，体细胞结构改变仍有待探索。为了提供全面的突变情况，我们对日本人群中 20 名 ESCC 患者的活检标本进行了全基因组测序 (WGS) 分析。 WGS 分析发现 ESCC 中 TP53、ZNF750 和 FAT1 的非沉默编码突变。我们在食管鳞癌中检测到六种突变特征，其中一种与吸烟状况显着相关。复发性结构变异（其中许多是染色体缺失）影响了 25%-30% 肿瘤中的 LRP1B、TTC28、CSMD1、PDE4D、SDKI 和 WWOX 等基因。鉴定出 11q13.3 (CCNDI)、3q26.33 (TP63/SOX2) 和 8p11.23 (FGFRI) 处的体细胞拷贝数扩增以及 9p21.3 (CDKN2A) 处的缺失。总体而言，这些基因组改变的多维观点提高了对食管鳞癌在分子水平上发展的理解，并为日本食管鳞癌的未来预后和治疗提供了启示。
Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in the Asian region, including Japan. A previous study reported mutational landscape of Japanese ESCCs by using exome sequencing. However, somatic structural alterations were yet to be explored. To provide a comprehensive mutational landscape, we performed whole genome sequencing (WGS) analysis of biopsy specimens from 20 ESCC patients in a Japanese population. WGS analysis identified non-silent coding mutations of TP53, ZNF750 and FAT1 in ESCC. We detected six mutational signatures in ESCC, one of which showed significant association with smoking status. Recurrent structural variations, many of which were chromosomal deletions, affected genes such as LRP1B, TTC28, CSMD1, PDE4D, SDKI and WWOX in 25%-30% of tumors. Somatic copy number amplifications at 11q13.3 (CCNDI), 3q26.33 (TP63/SOX2), and 8p11.23 (FGFRI) and deletions at 9p21.3 (CDKN2A) were identified. Overall, these multi-dimensional view of genomic alterations improve the understanding of the ESCC development at molecular level and provides future prognosis and therapeutic implications for ESCC in Japan.