Kluska Anna, Balabas Aneta, Piatkowska Magdalena, Czarny Katarzyna, Paczkowska Katarzyna, Nowakowska Dorota, Mikula Michal, Ostrowski Jerzy
Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland.
Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, 01-813, Warsaw, Poland.
BMC Med Genomics. 2017 Mar 9;10(1):14. doi: 10.1186/s12920-017-0251-8.
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.
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基因的种系失活突变与乳腺癌和卵巢癌风险增加相关。波兰乳腺癌和卵巢癌患者中复发性PALB2种系突变的患病率和谱尚未明确界定。
使用AmpliSeq技术从460例BRCA1/2突变阴性的家族性乳腺癌和/或卵巢癌以及早发性乳腺癌女性中扩增PALB2外显子，并在Ion Torrent PGM测序仪上进行测序。此外，在807例BRCA1/2突变阴性乳腺癌患者和1690例健康女性中，使用TaqMan分析对8个选定的变体进行基因分型。
鉴定出两个复发性PALB2突变，即c.172_175delTTGT和c.509_510delGA，以及一个新突变c.347insT。总共在7/460（1.5%）的患者中检测到PALB2致病突变。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体（SNV）。在另外一组807例患者中，鉴定出8例（1%）携带两个致病突变的携带者，即c.172_175delTTGT（0.5%）和c.509_510delGA（0.5%）。在健康对照中未鉴定出c.509_510delGA突变，而在4/1690（0.24%）的对照女性中鉴定出c.172_175delTTGT突变。
在波兰乳腺癌和/或卵巢癌患者中，观察到PALB2基因种系突变的频率约为1.5%。我们的研究证实了两个复发性PALB2突变；c.172_175delGA和c.509_510delGA。
