ena-STUDY-SKLB-11-05-2017-15:50:56:338-108
Whole-genome sequencing of signet ring cell carcinoma of gastric cancer
Gastric cancer is one of the most common cancers and leading cause of cancer mortality in the world, especially in China. Gastric signet-ring cell carcinoma (SRCC), defined as > 50% of signet-ring cells in the pathologic specimen, has a specific epidemiology and oncogenesis in gastric cancer. The prognosis of SRCC is still debated and appears to be stage-dependent. Generally, advanced SRCC is thought to have poorer treatment outcomes compared to non-SRCC. Although large effects have be taken to characterize the genetic profiles of gastric cancer including The Cancer Genome Atlas (TCGA) project no systematically investigation on SRCC has been done. we reviewed 1,868 gastric cancer patients with comprehensive clinic information enrolled in West China Hospital from 2006 and 2012, and preformed whole-genome sequencing (WGS) on 32 available SRCC tumor samples with >80% presence of signet-ring cells (defined as HSRCC) and their matched control. TP53 (28.1%), CDH1 (12.5%), and PIK3CA (12.5%) were the most frequently mutated gene, Recurrent somatic copy number alterations were observed in the region including FHIT (46.9% of loss), MYC (18.8% of gain), BCAS1 (15.6% of gain), and FGFR2 (12.5% of gain). Interestingly, high frequency (25%) of CLDN18-ARHGAP26/6 fusion were observed. To our knowledge, this is the first systematically clinical and genetic study on SRCC.
Gastric cancer is one of the most common cancers and leading cause of cancer mortality in the world, especially in China. Gastric signet-ring cell carcinoma (SRCC), defined as > 50% of signet-ring cells in the pathologic specimen, has a specific epidemiology and oncogenesis in gastric cancer. The prognosis of SRCC is still debated and appears to be stage-dependent. Generally, advanced SRCC is thought to have poorer treatment outcomes compared to non-SRCC. Although large effects have be taken to characterize the genetic profiles of gastric cancer including The Cancer Genome Atlas (TCGA) project no systematically investigation on SRCC has been done. we reviewed 1,868 gastric cancer patients with comprehensive clinic information enrolled in West China Hospital from 2006 and 2012, and preformed whole-genome sequencing (WGS) on 32 available SRCC tumor samples with >80% presence of signet-ring cells (defined as HSRCC) and their matched control. TP53 (28.1%), CDH1 (12.5%), and PIK3CA (12.5%) were the most frequently mutated gene, Recurrent somatic copy number alterations were observed in the region including FHIT (46.9% of loss), MYC (18.8% of gain), BCAS1 (15.6% of gain), and FGFR2 (12.5% of gain). Interestingly, high frequency (25%) of CLDN18-ARHGAP26/6 fusion were observed. To our knowledge, this is the first systematically clinical and genetic study on SRCC.