Department of Molecular Pathology, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland.
BMC Med Genet. 2010 Feb 2;11:20. doi: 10.1186/1471-2350-11-20.
PALB2 protein was recently identified as a partner of BRCA1 and BRCA2 which determines their proper function in DNA repair.
Initially, the entire coding sequence of the PALB2 gene with exon/intron boundaries was evaluated by the PCR-SSCP and direct sequencing methods on 70 ovarian carcinomas. Sequence variants of interest were further studied on enlarged groups of ovarian carcinomas (total 339 non-consecutive ovarian carcinomas), blood samples from 334 consecutive sporadic and 648 consecutive familial breast cancer patients, and 1310 healthy controls from central Poland.
Ten types of sequence variants were detected, and among them four novel polymorphisms: c.2996+58T>C in intron 9; c.505C>A (p.L169I), c.618T>G (p.L206L), both in exon 4; and c.2135C>T (A712V) in exon 5 of the PALB2 gene. Another two polymorphisms, c.212-58A>C and c.2014G>C (E672Q) were always detected together, both in cancer (7.5% of patients) and control samples (4.9% of controls, p = 0.2). A novel germline truncating mutation, c.509_510delGA (p.R170fs) was found in exon 4: in 2 of 339 (0.6%) unrelated ovarian cancer patients, in 4 of 648 (0.6%) unrelated familial breast cancer patients, and in 1 of 1310 controls (0.08%, p = 0.1, p = 0.044, respectively). One ovarian cancer patient with the PALB2 mutation had also a germline nonsense mutation of the BRCA2 gene.
The c.509_510delGA is a novel PALB2 mutation that increases the risk of familial breast cancer. Occurrence of the same PALB2 alteration in seven unrelated women suggests that c.509_510delGA (p.R170fs) is a recurrent mutation for Polish population.
PALB2 蛋白最近被鉴定为 BRCA1 和 BRCA2 的伴侣，决定了它们在 DNA 修复中的正常功能。
最初，通过 PCR-SSCP 和直接测序方法评估了 PALB2 基因的整个编码序列及其外显子/内含子边界，共评估了 70 例卵巢癌。在更大的卵巢癌组（共 339 例非连续卵巢癌）、334 例连续散发性和 648 例连续家族性乳腺癌患者的血液样本以及来自波兰中部的 1310 例健康对照中进一步研究了感兴趣的序列变异。
检测到十种类型的序列变异，其中包括四种新的多态性：9 号内含子中的 c.2996+58T>C；4 号外显子中的 c.505C>A(p.L169I)和 c.618T>G(p.L206L)；以及 5 号外显子中的 c.2135C>T(A712V)。另外两种多态性 c.212-58A>C 和 c.2014G>C(E672Q)总是一起检测到，在癌症（7.5%的患者）和对照样本（4.9%的对照，p=0.2）中均有发现。在 339 例（0.6%）无关联卵巢癌患者、648 例（0.6%）无关联家族性乳腺癌患者和 1310 例（0.08%）对照中发现了一种新的胚系截短突变 c.509_510delGA(p.R170fs)，分别为 2 例（0.6%）、4 例（0.6%）和 1 例（0.08%），（p=0.1，p=0.044）。一名携带 PALB2 突变的卵巢癌患者还携带 BRCA2 基因的胚系无义突变。
c.509_510delGA 是一种新的 PALB2 突变，增加了家族性乳腺癌的风险。七位无关联女性中出现相同的 PALB2 改变表明 c.509_510delGA(p.R170fs)是波兰人群中的一种复发性突变。
