Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
University of Genoa, Ospedale Policlinico San Martino-IRCCS, Genova, Italy.
Oncogene. 2022 Jun;41(26):3455-3460. doi: 10.1038/s41388-022-02350-6. Epub 2022 May 26.
Signet ring cell carcinoma (SRCC) is rare: about 10% of gastric cancer (GC) and 1% of colorectal cancer (CRC). SRCC is associated with poor prognosis, however the underlying molecular characteristics are unknown. SRCCs were analyzed using NGS, immunohistochemistry, and in situ hybridization. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. A total of 8500 CRC and 1100 GC were screened. Seventy-six SRCC were identified from the CRC cohort (<1%) and 98 from the GC cohort (9%). The most frequently mutated genes in CRC-SRCC were TP53 (47%), ARID1A (26%), APC (25%); in GC-SRCC were TP53 (42%), ARID1A (27%), CDH1 (11%). When compared to non-SRCC histology (N = 3522), CRC-SRCC (N = 37) more frequently had mutations in BRCA1 (11% vs 1%, P < 0.001) and less frequently mutations in APC (19% vs 78%, P < 0.001), KRAS (22% vs 51%, P = 0.001) and TP53 (47% vs 73%, P = 0.001). Among the GC cohort, SRCC (N = 54) had a higher frequency of mutations in CDH1, BAP1, and ERBB2, compared to non-SRCC (N = 540). Our data suggest that SRCCs harbor a similar molecular profile, regardless of the tumor location. Tailored therapy may become available for these patients.
印戒细胞癌（SRCC）较为罕见：约占胃癌（GC）的 10%和结直肠癌（CRC）的 1%。SRCC 与预后不良相关，但潜在的分子特征尚不清楚。本研究采用 NGS、免疫组织化学和原位杂交技术对 SRCC 进行分析。根据体细胞非同义错义突变计算肿瘤突变负担（TMB），并通过已知微卫星不稳定（MSI）位点的 NGS 评估 MSI。共筛选了 8500 例 CRC 和 1100 例 GC。在 CRC 队列中发现了 76 例 SRCC（<1%），在 GC 队列中发现了 98 例（9%）。CRC-SRCC 中最常突变的基因是 TP53（47%）、ARID1A（26%）、APC（25%）；GC-SRCC 中最常突变的基因是 TP53（42%）、ARID1A（27%）、CDH1（11%）。与非 SRCC 组织学（N=3522）相比，CRC-SRCC（N=37）中 BRCA1 突变的频率更高（11% vs. 1%，P<0.001），APC 突变的频率更低（19% vs. 78%，P<0.001），KRAS 突变的频率更低（22% vs. 51%，P=0.001），TP53 突变的频率更低（47% vs. 73%，P=0.001）。在 GC 队列中，与非 SRCC（N=540）相比，SRCC（N=54）中 CDH1、BAP1 和 ERBB2 突变的频率更高。我们的数据表明，无论肿瘤部位如何，SRCC 都具有相似的分子特征。这些患者可能会有针对性的治疗方法。
