Cortesi Laura, Turchetti Daniela, Bertoni Chiara, Zanocco-Marani Tommaso, Vinceti Marco, Silvestri Chiara, Federico Massimo, Silingardi Vittorio, Ferrari Sergio
Dipartimento di Oncologia ed Ematologia, Universitá di Modena e Reggio Emilia, Italy.
Eur J Hum Genet. 2003 Mar;11(3):210-4. doi: 10.1038/sj.ejhg.5200948.
Hereditary breast/ovarian cancer is a well-characterized clinical entity, largely attributed to the inheritance of BRCA1 or BRCA2 mutations. Among general population, the mutation's frequency of these genes is very low; therefore, the identification of two independent mutations in the same family is a rare event. This study reports the presence of two mutations, one in the BRCA1 and the second in the BRCA2 gene in an Italian Caucasian kindred. This family is composed of more than 250 individuals, spanning through five generations, among which endogamy was a common phenomenon. Considering the tumor spectrum, this family is characterized by a high incidence of different types of cancer. In our study, we considered only three out of seven family units for BRCA1 and BRCA2 analysis. In one of the family units, we found independent mutations of both BRCA genes. The BRCA1 mutation on exon 11 (3358T-->A) was identified originally in the index case and subsequently in 18 members of this family, whereas the same mutation was not detected in a related family member with male breast cancer. The male breast cancer patient led to the identification, through mutational analysis, of a new BRCA2 mutation (8756delA). This BRCA2 mutation was also found in the male breast cancer patient's daughter. The discovery of the BRCA2 mutation allowed us to alert the patient's daughter who, otherwise, could be falsely reassured since she had a negative BRCA1 test.
遗传性乳腺癌/卵巢癌是一种特征明确的临床实体，很大程度上归因于BRCA1或BRCA2基因突变的遗传。在普通人群中，这些基因的突变频率非常低；因此，在同一家族中鉴定出两个独立的突变是罕见事件。本研究报告了一个意大利白种人家族中存在两个突变，一个在BRCA1基因，另一个在BRCA2基因。这个家族由250多名个体组成，跨越五代，其中近亲结婚是常见现象。考虑到肿瘤谱，这个家族的特点是不同类型癌症的发病率很高。在我们的研究中，我们仅对七个家族单元中的三个进行了BRCA1和BRCA2分析。在其中一个家族单元中，我们发现了两个BRCA基因的独立突变。外显子11上的BRCA1突变（3358T→A）最初在索引病例中被鉴定出来，随后在该家族的18名成员中也被发现，而在一名患有男性乳腺癌的相关家族成员中未检测到相同突变。通过突变分析，这名男性乳腺癌患者导致鉴定出一个新的BRCA2突变（8756delA）。这个BRCA2突变也在该男性乳腺癌患者的女儿中被发现。BRCA2突变的发现使我们能够提醒患者的女儿，否则她可能会因为BRCA1检测呈阴性而得到错误的安心。
