Chan Sock Hoai, Chiang Jianbang, Ngeow Joanne
Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 169610, Singapore.
Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, 169857, Singapore.
Hered Cancer Clin Pract. 2021 Mar 25;19(1):21. doi: 10.1186/s13053-021-00178-x.
Although CDKN2A is well-known as a susceptibility gene for melanoma and pancreatic cancer, germline variants have also been anecdotally associated with a broader range of neoplasms including neural system tumors, head and neck squamous cell carcinomas, breast carcinomas, as well as sarcomas. The CDKN2A gene encodes for two distinct tumor suppressor proteins, p16 and p14, however, the independent association of germline alterations affecting these two proteins with cancer is under-appreciated. Here, we reviewed CDKN2A germline alterations reported among individuals and families with cancer in the literature, specifically addressing the cancer phenotypes in relation to the molecular consequence on p16 and p14. While melanoma is observed to associate with variants affecting both p16 and p14 transcripts, it is noted that variants affecting p14 are more frequently observed with a heterogenous range of cancers. Finally, we reflected on the implications of this inferred genotype-phenotype association in clinical practice and proposed that clinical management of CDKN2A germline variant carriers should involve dedicated cancer genetics services, with multidisciplinary input from various healthcare professionals.
尽管CDKN2A作为黑色素瘤和胰腺癌的易感基因广为人知，但种系变异也一直被传闻与更广泛的肿瘤相关，包括神经系统肿瘤、头颈部鳞状细胞癌、乳腺癌以及肉瘤。CDKN2A基因编码两种不同的肿瘤抑制蛋白p16和p14，然而，影响这两种蛋白的种系改变与癌症的独立关联尚未得到充分认识。在此，我们回顾了文献中报道的癌症个体和家族中的CDKN2A种系改变，特别探讨了与p16和p14分子后果相关的癌症表型。虽然观察到黑色素瘤与影响p16和p14转录本的变异有关，但值得注意的是，影响p14的变异在多种不同类型的癌症中更常见。最后，我们思考了这种推断的基因型-表型关联在临床实践中的意义，并提出CDKN2A种系变异携带者的临床管理应包括专门的癌症遗传学服务，并由各医疗专业人员提供多学科投入。
