A novel germline PALB2 deletion in Polish breast and ovarian cancer patients.
A novel germline PALB2 deletion in Polish breast and ovarian cancer patients.
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DOI：
10.1186/1471-2350-11-20
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发表时间：
2010-02-02
影响因子：
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通讯作者：
Kupryjanczyk J
中科院分区：
文献类型：
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作者：
Dansonka-Mieszkowska A;Kluska A;Moes J;Dabrowska M;Nowakowska D;Niwinska A;Derlatka P;Cendrowski K;Kupryjanczyk J
最近发现PALB2蛋白是BRCA1和BRCA2的配对蛋白，这决定了它们在DNA修复中的适当功能。首先，用聚合酶链式反应-单链构象多态性和直接测序的方法对70例卵巢癌PALB2基因的编码序列进行了分析。对扩大的卵巢癌组(总共339例非连续性卵巢癌)、334例连续的散发性乳腺癌患者和648例连续的家族性乳腺癌患者的血液样本以及来自波兰中部的1310名健康对照进行了感兴趣的序列变异进一步研究。检测到10种类型的序列变异，其中有4种新的多态：位于第9内含子的c.2996+58T>；C；位于外显子4的c.505C>；A(p.L169I)；c.618T>；G(p.L206L)；以及位于外显子5的c.2135C>；T(A712V)。另外两个基因c.212-58A>；C和c.2014G>；C(E672Q)在癌症患者(7.5%)和对照组(4.9%，p=0.2)中同时检测到。在外显子4中发现了一种新的种系截断突变c.509_510delGA(p.R170fs)：在339例无亲缘关系的卵巢癌患者中有2例(0.6%)，在4例无亲缘关系的家族性乳腺癌患者中有4例(0.6%)，在1,310名对照组中有1例(0.08%，p=0.1，p=0.044)。一名带有PALB2突变的卵巢癌患者也有BRCA2基因的胚系无义突变。C.509_510delGA是一种新的PALB2突变，可增加家族性乳腺癌的风险。在7名无血缘关系的女性中发生相同的PALB2改变，表明C.509_510delGA(p.R170fs)是波兰人群的一种经常性突变。
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.