神经内分泌肿瘤（NENs）是一组分布在不同器官的异质性肿瘤，其特征性遗传异常尚未确定。基于对包含33种癌症亚型的9193名患者乳腺癌基因组图谱数据库进行的分析，我们发现在8例胰腺神经内分泌癌中有7例（87.5%）和170例胰腺导管腺癌（PDACs）中有20例（11.76%）中出现了含有Box 6/Box 7的FAK变体（FAK6/7）。我们对157例中国患者的胰腺肿瘤样本进行了FAK变异的检测，发现在45例胰腺NENs中有34例（75.6%），40例胰腺实性假乳头状肿瘤中有19例（47.5%），和69例PDACs中有2例（2.9%）呈FAK6/7阳性。我们还对乳腺神经内分泌癌（BrNECs）进行了FAK片段变异的测试，发现在15例BrNECs中有14例（93.3%）呈FAK6/7阳性，而在23例非-NEC乳腺癌中则没有阳性样本。我们探讨了潜在的机制并发现，在FAK6/7阳性的胰腺肿瘤和乳腺肿瘤中，有一个剪接因子丝氨酸/精氨酸重复基质蛋白4（SRRM4）的过度表达，促进了细胞中FAK6/7的形成。这些结果提示FAK6/7可能是NENs的生物标记物，并可能成为这些孤立疾病的潜在治疗靶点。 © 2023. 高等教育出版社。

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.© 2023. Higher Education Press.