PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland.
PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland.
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DOI：
10.1186/s12920-017-0251-8
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发表时间：
2017-03-09
影响因子：
2.7
通讯作者：
Ostrowski J
中科院分区：
文献类型：
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作者：
Kluska A;Balabas A;Piatkowska M;Czarny K;Paczkowska K;Nowakowska D;Mikula M;Ostrowski J
PALB2基因编码一种在维持基因组完整性方面起关键作用的蛋白质。PALB2种系失活突变与乳腺癌和卵巢癌风险增加有关。波兰乳腺癌和卵巢癌患者中复发PALB2种系突变的患病率和谱尚不明确。使用AmpliSeq技术从460名brca1 /2突变阴性的家族性乳腺癌和/或卵巢癌和早发性乳腺癌患者中扩增PALB2外显子，并在Ion Torrent PGM测序仪上测序。此外，在807名brca1 /2突变阴性乳腺癌患者和1690名健康女性中，使用TaqMan法对8个选定的变异进行了基因分型。发现了两个复发性PALB2突变，c.172_175delTTGT和c.509_510delGA，以及一个新的突变，c.347insT。总共有7/460例（1.5%）患者检测到PALB2致病性突变。此外，在乳腺癌和/或卵巢癌患者中，在PALB2编码区检测到几个单核苷酸变异（snv）。在另一组807例患者中，鉴定出8例（1%）携带两种致病突变，c.172_175delTTGT（0.5%）和c.509_510delGA（0.5%）。在健康对照中未发现c.509_510delGA突变，而在4/1690（0.24%）的对照女性中发现c.172_175delTTGT突变。在波兰乳腺癌和/或卵巢癌患者中，PALB2基因的种系突变频率约为1.5%。我们的研究证实了两种复发性PALB2突变；c.172_175delGA和c.509_510delGA。
The PALB2 gene encodes a protein that plays a crucial role in maintaining genomic integrity. Germline inactivating mutations in PALB2 are associated with an increased risk of breast and ovarian cancer. The prevalence and spectrum of recurrent PALB2 germline mutations in breast and ovarian cancer patients from Poland is not clearly defined. PALB2 exons were amplified from 460 BRCA1/2-mutation negative women with familial breast and/or ovarian cancer and early-onset breast cancer using AmpliSeq technology and sequenced on an Ion Torrent PGM sequencer. In addition, eight selected variants were genotyped using TaqMan assays in 807 BRCA1/2-mutation negative breast cancer patients and 1690 healthy women. Two recurrent PALB2 mutations, c.172_175delTTGT and c.509_510delGA, were identified, along with one novel mutation, c.347insT. In total, PALB2 pathogenic mutations were detected in 7/460 (1.5%) patients. Furthermore, in breast and/or ovarian cancer patients, several single nucleotide variants (SNVs) were detected in the PALB2 coding region. In an additional group of 807 patients, eight (1%) carriers of two pathogenic mutations, c.172_175delTTGT (0.5%) and c.509_510delGA (0.5%), were identified. The c.509_510delGA mutation was not identified in healthy controls, while c.172_175delTTGT was identified in 4/1690 (0.24%) of control women. Germline mutations in the PALB2 gene were observed at a frequency of approximately 1.5% in Polish breast and/or ovarian cancer patients. Our study confirms two recurrent PALB2 mutations; c.172_175delGA and c.509_510delGA.