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 oncog...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(FAK^(6/7))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 FAK^(6/7)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 FAK^(6/7)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 FAK^(6/7)-positive pancreatic tumors and breast tumors,which promoted the formation of FAK^(6/7)in cells.These results suggested that FAK^(6/7)could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.展开更多
基金supported by the Key Project of the National Natural Science Foundation of China (No.81830093)the National Key Research and Development Program of China (Nos.2020YFC2002705,2020YFA0803300,and 2022YFA1103900)+2 种基金the CAMS Innovation Fund for Medical Sciences (CIFMS,Nos.2022-RC310-05 and 2021-RC310-003)the CAMS Initiative for Innovative Medicine (Nos.2021-12M-1-014,2022-I2M-2-001,and 2021-12M-1-021)the National Natural Science Foundation of China (Nos.82073092 and 82273076).
文摘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(FAK^(6/7))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 FAK^(6/7)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 FAK^(6/7)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 FAK^(6/7)-positive pancreatic tumors and breast tumors,which promoted the formation of FAK^(6/7)in cells.These results suggested that FAK^(6/7)could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
