Gastric cancer (GC) is one of the most common lethal malignancies worldwide. Signet ring cell carcinoma (SRCC) is a poorly differentiated gastric cancer. The molecular characteristics and prognostic of SRCC are not well studied.
Formalin fixed paraffin embedded (FFPE) samples of 64 Chinese solid tumor patients were collected for next‐generation sequencing (NGS) based 450 genes panel assay. Genomic alterations including single base substitution, short and long insertions/deletions, copy number variations, gene fusions and rearrangement were assessed. Microsatellite stable (MSS) status and TMB (tumor mutational burden) were also acquired by an NGS algorithm.
A total of 64 patients were identified as GC-SRCC through SRCC histology. The most frequently mutated genes were TP53(48%), CDH1(31%), ARID1A(14%), CDKN2A(9%), LRP1B(9%), KMT2D(6%), NF1(6%), ERBB2(9%) and GLI3(8%). Meanwhile, the copy numbers of FGFR2(14%), FGF3(8%), FGF19(8%), FGF4(8%), MYC(8%), CCND1(6%) and CDKN2A(9%) were frequently altered in SRCC.FGFR2 and 11q13 amplification is the first time reported in Chinese SRCC. Moreover, FGFR2 rearrangement (FGFR2/VTI1A and FGFR2/TACC2) was detected in 4% tumor samples. 34 cases had received chemotherapy, 4 cases had confirmed partial responses (PR); 14 cases had reached the stability of disease (SD). Noticeably, patients harboring gene rearrangement (N = 9) were observed a much shorter overall survival time (OS) in comparison with patients without any gene rearrangement (N = 14) (13.2 months vs 24.2 months, P < 0.05). Additionally, patients with CDH1 mutation (N = 9) showed a shorter OS than CDH1 wide type (N = 25) (14.2 months vs 25.3 months, P = 0.11), although the difference was not statistically significant.
Our observation reveals the molecular characteristics of SRCC. Gene rearrangements might associate to shorter OS. FGFR2 and 11q13 region amplification were newly observed in SRCC. It might provide new possibilities for the treatment of SRCC. Due to the limitations of the number of samples, the results may require further research and validation.
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All authors have declared no conflicts of interest.