Tricarico Rossella, Bet Paola, Ciambotti Benedetta, Di Gregorio Carmela, Gatteschi Beatrice, Gismondi Viviana, Toschi Benedetta, Tonelli Francesco, Varesco Liliana, Genuardi Maurizio
Department of Clinical Pathophysiology, Medical Genetics Unit, University of Florence Medical School, Viale G. Pieraccini 6, 50139 Florence, Italy.
Cancer Lett. 2009 Feb 18;274(2):266-70. doi: 10.1016/j.canlet.2008.09.022. Epub 2008 Nov 5.
MUTYH-associated polyposis (MAP) is an autosomal recessive condition predisposing to colorectal cancer, caused by constitutional biallelic mutations in the base excision repair (BER) gene MUTYH. Colorectal tumours from MAP patients display an excess of somatic G>T mutations in the APC and KRAS genes due to defective BER function. To date, few extracolonic manifestations have been observed in MAP patients, and the clinical spectrum of this condition is not yet fully established. Recently, one patient with a diagnosis of endometrial cancer and biallelic MUTYH mutations has been described. We here report on two additional unrelated MAP patients with biallelic MUTYH germline mutations who developed endometrioid endometrial carcinoma. The endometrial tumours were evaluated for PTEN, PIK3CA, KRAS, BRAF and CTNNB1 mutations. A G>T transversion at codon 12 of the KRAS gene was observed in one tumour. A single 1bp frameshift deletion of PTEN was observed in the same sample. Overall, these findings suggest that endometrial carcinoma is a phenotypic manifestations of MAP and that inefficient repair of oxidative damage can be involved in its pathogenesis.
MUTYH相关息肉病（MAP）是一种常染色体隐性疾病，易患结直肠癌，由碱基切除修复（BER）基因MUTYH的双等位基因胚系突变引起。由于BER功能缺陷，MAP患者的结直肠肿瘤在APC和KRAS基因中表现出过量的体细胞G>T突变。迄今为止，在MAP患者中很少观察到结肠外表现，这种疾病的临床谱尚未完全明确。最近，有一例诊断为子宫内膜癌且存在双等位基因MUTYH突变的患者被报道。我们在此报告另外两名不相关的MAP患者，他们携带双等位基因MUTYH胚系突变，发生了子宫内膜样子宫内膜癌。对子宫内膜肿瘤进行了PTEN、PIK3CA、KRAS、BRAF和CTNNB1突变检测。在一个肿瘤中观察到KRAS基因第12密码子处发生了G>T颠换。在同一样本中观察到PTEN有一个单碱基1bp移码缺失。总体而言，这些发现表明子宫内膜癌是MAP的一种表型表现，氧化损伤修复效率低下可能参与其发病机制。
