Infante Mar, Durán Mercedes, Esteban-Cardeñosa Eva, Miner Cristina, Velasco Eladio
Laboratorio de Genética del Cáncer, Instituto de Biología y Genética Molecular, Universidad de Valladolid, Sanz y Forés s/n, 47003 Valladolid, Spain.
J Hum Genet. 2006;51(7):611-7. doi: 10.1007/s10038-006-0404-7. Epub 2006 Jun 7.
A total of 264 unrelated breast/ovarian cancer patients and 45 healthy individuals with familial antecedents referred for genetic testing were scanned for germ-line mutations in BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis (CSGE) and heteroduplex analysis by capillary array electrophoresis (HA-CAE). We detected 101 distinct mutations (41 in BRCA1 and 60 in BRCA2); ten of them have not been previously reported. These mutations were c.2411_2429dup19, c.2802_2805delCAAA and c.5294A>G (p.E1725E) of BRCA1; and c.667C>T (p.Q147X), c.2683C>T (p.Q819X), c.5344_5347delAATA, c.5578_5579delAA;insT, c.8260_8261insGA, c.744+14C>T and c.8099A>G (p.Y2624C) of BRCA2. Twenty-four different mutations, including seven of the new mutations (five frameshift and two nonsense), were classified as pathogenic. These 24 alterations were found in 39 families (12.6% of all families). A remarkable proportion of deleterious mutations were found in BRCA2: 25 families carried a mutation in BRCA2 (BRCA2+; 64.1%) compared with 14 families BRCA1+ (35.9%). The highest incidences of deleterious mutations were found in families with three or more cases of site-specific breast cancer (BC) (27.4%) and families with BC and ovarian cancer (22.2%). Finally, four recurrent mutations, 3036_3039delACAA, c.5374_5377delTATG of BRCA2, as well as c.5272-1G>A and c.5242C>A (p.A1708E) of BRCA1, accounted for 44% of all of the deleterious mutations.
共有264名无血缘关系的乳腺癌/卵巢癌患者以及45名有家族病史且前来进行基因检测的健康个体，通过构象敏感凝胶电泳（CSGE）和毛细管阵列电泳异源双链分析（HA-CAE）对BRCA1和BRCA2基因的种系突变进行扫描。我们检测到101种不同的突变（BRCA1基因中有41种，BRCA2基因中有60种）；其中10种此前未曾报道过。这些突变分别是BRCA1基因的c.2411_2429dup19、c.2802_2805delCAAA和c.5294A>G（p.E1725E）；以及BRCA2基因的c.667C>T（p.Q147X）、c.2683C>T（p.Q819X）、c.5344_5347delAATA、c.5578_5579delAA;insT、c.8260_8261insGA、c.744+14C>T和c.8099A>G（p.Y2624C）。24种不同的突变，包括7种新突变（5种移码突变和2种无义突变），被归类为致病性突变。这24种改变在39个家族中被发现（占所有家族的12.6%）。在BRCA2基因中发现了相当比例的有害突变：25个家族携带BRCA2基因突变（BRCA2+；64.1%），而携带BRCA1基因突变的家族有14个（35.9%）。在有三例或更多例特定部位乳腺癌（BC）的家族（27.4%）以及有乳腺癌和卵巢癌的家族（22.2%）中，有害突变的发生率最高。最后，BRCA2基因的四种重复突变，即3036_3039delACAA、c.5374_5377delTATG，以及BRCA1基因的c.5272-1G>A和c.5242C>A（p.A1708E），占所有有害突变的44%。
