Monnerat Christian, Chompret Agnès, Kannengiesser Caroline, Avril Marie-Françoise, Janin Nicolas, Spatz Alain, Guinebretière Jean-Marc, Marian Catalin, Barrois Michel, Boitier Françoise, Lenoir Gilbert M, Bressac-de Paillerets Brigitte
Department of Genetics, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif Cedex, France.
Fam Cancer. 2007;6(4):453-61. doi: 10.1007/s10689-007-9143-y. Epub 2007 Jul 12.
From epidemiological studies it appears that breast cancer (BC) and cutaneous melanoma (CMM) in the same individual occur at a higher frequency than expected by chance. Genetic factors common to both cancers can be suspected. Our goal was to estimate the involvement of "high risk" genes in patients presenting these two neoplasia, selected irrespectively from family history and age at diagnosis.
Eighty two patients with BC and CMM were screened for BRCA1, BRCA2, TP53, CDKN2A and CDK4 (exon 2) germline mutations.
Deleterious mutations were identified in 6 patients: two carriers of a BRCA1 germline mutation, two carriers of TP53 germline mutations (one of which also harbored a BRCA2 deleterious mutation, the other one a BRCA2 unclassified variant), and two carriers of a CDKN2A germline mutation. In addition, 6 variants of unknown signification were identified in BRCA1 or BRCA2 genes. Regarding family history, 3/13 (23%) patients with a positive family history of BC or CMM were carriers of a germline mutation, whereas only 3/69 (4%) patients without family history were carriers of a germline mutation.
Our findings show that few patients with BC and CMM who lacked family histories of these cancers are carriers of deleterious germline mutations in four of the five genes we examined. We describe for the first time, two simultaneous BRCA2 and TP53 mutations, suggesting that analysis in more than one gene could be performed if a patient's personal or familial history does not match a single syndrome.
从流行病学研究来看，同一患者同时发生乳腺癌（BC）和皮肤黑色素瘤（CMM）的频率似乎高于偶然预期。可以推测这两种癌症存在共同的遗传因素。我们的目标是评估“高风险”基因在患有这两种肿瘤的患者中的作用，这些患者的选择与家族病史和诊断年龄无关。
对82例患有乳腺癌和皮肤黑色素瘤的患者进行了BRCA1、BRCA2、TP53、CDKN2A和CDK4（第2外显子）种系突变的筛查。
在6例患者中鉴定出有害突变：2例携带BRCA1种系突变，2例携带TP53种系突变（其中1例还携带BRCA2有害突变，另1例携带BRCA2未分类变异），以及2例携带CDKN2A种系突变。此外，在BRCA1或BRCA2基因中鉴定出6个意义不明的变异。关于家族病史，13例有乳腺癌或皮肤黑色素瘤家族史阳性的患者中有3例（23%）是种系突变携带者，而69例无家族史的患者中只有3例（4%）是种系突变携带者。
我们的研究结果表明，在我们检测的五个基因中，很少有缺乏这些癌症家族史的乳腺癌和皮肤黑色素瘤患者是有害种系突变的携带者。我们首次描述了两个同时存在的BRCA2和TP53突变，这表明如果患者的个人或家族病史与单一综合征不匹配，可以对多个基因进行分析。
