背景技术癌症是依赖于遗传和环境因素的影响的多因素疾病。大约10%的癌症与种系突变有关,容易患癌症的风险更高。目前,识别易感性和/或关联基因癌症的小组的使用已经越来越多地被使用,在临床实践和科学研究中。目的调查巴西东北部地区具有遗传性癌症特征的患者的基因突变。在那里,内源性和近亲婚姻的频率很高。方法一组17个基因(BRCA1,BRCA2,APC,TP53,PTEN,RET,VHL,RB1,CDKN2,CDH1,CHEK2,MLH1,MSH2,MSH6,MUTYH,XPA,和XPC)与癌症和遗传综合征相关的分析。评估了15例遗传性癌症患者。结果发现的致病变异为c.187G>A(p。Gly396Asp),MUTYH基因中的rs36053993在一名男性患者中诊断为黑色素瘤,年龄为43岁,并且有该肿瘤的家族史。该基因编码一种与DNA修复相关的重要酶,并与其他类型的癌症有关。这是关于黑色素瘤的第一份报告,一旦MUTYH蛋白在皮肤组织中表达并负责修复引起的损伤,例如,通过阳光照射。结论本研究结果表明,该突变可能是黑色素瘤遗传易感性的重要因素。但是需要对这种突变进行更广泛的调查。
Introduction Cancer is a multifactorial disease dependent on the influence of genetic and environmental factors. About 10% of cancers are associated with germline mutations, which predispose to a higher risk of developing cancer. Currently, the use of panels that identify susceptibility and/or association genes cancer has been increasingly used, both in clinical practice and in scientific research. Objective To investigate genetic mutations in patients with a profile for hereditary cancer in individuals from a region of northeast Brazil, where there is a high frequency of endogenous and consanguineous marriages. Methods A set of 17 genes ( BRCA1 , BRCA2 , APC , TP53 , PTEN , RET , VHL , RB1 , CDKN2 , CDH1 , CHEK2 , MLH1 , MSH2 , MSH6 , MUTYH , XPA , and XPC ) associated with cancer and hereditary syndromes were analyzed. Fifteen patients with a hereditary cancer profile were evaluated. Results The pathogenic variant found was c.1187G > A (p.Gly396Asp), rs36053993 in the MUTYH gene in a male patient diagnosed with melanoma at the age of 43 years and a family history for this tumor. This gene encodes an important enzyme related to DNA repair and has been associated with other types of cancer, this is the first report of an association with melanoma, the biological plausibility of this association is given once the MUTYH protein is expressed in the skin tissue and is responsible for repairing damage caused, for example, by sun exposure. Conclusion The results of this study suggest that this mutation may be important for the hereditary predisposition to melanoma, but a broader investigation of this mutation is needed.