Esteban Cardeñosa Eva, Bolufer Gilabert Pascual, Palanca Suela Sarai, Barragán González Eva, Oltra Soler Silvestre, Chirivella González Isabel, Segura Huerta Angel, Guillén Ponce Carmen, Martínez de Dueñas Eduardo, Cuevas Cuerda Dolores, Salas Trejo Dolores
Laboratorio de Biología Molecular, Servicio de Biopatología Clínica, Hospital Universitario La Fe, Valencia. España.
Med Clin (Barc). 2008 Feb 9;130(4):121-6. doi: 10.1157/13115767.
The objective of the present study was to investigate the mutational spectrum of BRCA1 and BRCA2 in the Valencian Community, comparing this spectrum with that reported in Spain. We also analyze the association of the mutations with the family history of the selected families.
We analyzed the mutations in the BRCA1 and BRCA2 in 147 families with history of breast and/or ovarian cancer. The detection was based on the amplification of in frame and flanking regions of BRCA1 and BRCA2 genes by polymerase chain reaction, detection of the heteroduplex formed by conformation-sensitive gel electrophoresis and their characterization by sequencing.
We identified 24 different pathogenic mutations in 50 out of the 147 families (34.0%; 23 in BRCA1 and 27 in BRCA2). The higher incidence of pathogenic mutations was observed in families with breast and ovarian cancer or with more than 3 cases of breast cancer. The most frequent mutations in BRCA1 were the c.187_188delAG, c.2080delA and the c.3889_3890delAG, whereas for BRCA2 the mutations with higher prevalence was observed for c.9254_9258delATCAT and the c.9204delCATCAGATTTATAT. We detected 5 pathogenic mutations (p.Y1429X in BRCA1 and c.1835insT, c.5025delT, c.6722delT and p.Q3156X in BRCA2) not reported in the Breast Cancer Information Core Database. Among them, the BRCA2 mutations c.1835insT and c.5025delT were recurrent and seemed to be characteristic of the population the Valencian Community.
We detected pathogenic mutations in BRCA1 and BRCA2 genes in 34.0% of the families studied. The mutations c.1835insT and c.5025delT were 2 new recurrent pathogenic mutations in BRCA2 that seemed to be characteristic of the population of the Valencian Community. The study reports 5 new pathogenic mutations to the world spectrum of BRCA1 and BRCA2 mutations and other 5 mutations to the Spanish spectrum.
本研究的目的是调查瓦伦西亚自治区BRCA1和BRCA2的突变谱，并将此谱与西班牙报道的进行比较。我们还分析了这些突变与所选家族家族史的关联。
我们分析了147个有乳腺癌和/或卵巢癌家族史的家族中BRCA1和BRCA2的突变。检测基于通过聚合酶链反应扩增BRCA1和BRCA2基因的框内和侧翼区域，通过构象敏感凝胶电泳检测形成的异源双链体并通过测序对其进行表征。
我们在147个家族中的50个家族中鉴定出24种不同的致病突变（34.0%；BRCA1中有23种，BRCA2中有27种）。在患有乳腺癌和卵巢癌或有超过3例乳腺癌病例的家族中观察到致病突变的发生率更高。BRCA1中最常见的突变是c.187_188delAG、c.2080delA和c.3889_3890delAG，而对于BRCA2，c.9254_9258delATCAT和c.9204delCATCAGATTTATAT的突变发生率较高。我们检测到5种致病突变（BRCA1中的p.Y1429X以及BRCA2中的c.1835insT、c.5025delT、c.6722delT和p.Q3156X）未在乳腺癌信息核心数据库中报道。其中，BRCA2突变c.1835insT和c.5025delT是复发性的，似乎是瓦伦西亚自治区人群的特征。
我们在所研究的34.0%的家族中检测到BRCA1和BRCA2基因的致病突变。c.1835insT和c.5025delT突变是BRCA2中2种新的复发性致病突变，似乎是瓦伦西亚自治区人群的特征。该研究向世界BRCA1和BRCA2突变谱报告了5种新的致病突变，并向西班牙谱报告了另外5种突变。
