A novel germline <it>PALB2 </it>deletion in Polish breast and ovarian cancer patients

• Main Authors: Cendrowski Krzysztof, Derlatka Pawel, Niwinska Anna, Nowakowska Dorota, Dabrowska Michalina, Moes Joanna, Kluska Anna, Dansonka-Mieszkowska Agnieszka, Kupryjanczyk Jolanta
• Format: Article
• Language: English
• Published: BMC 2010-02-01
• Series: BMC Medical Genetics
• Online Access: http://www.biomedcentral.com/1471-2350/11/20

<p>Abstract</p> <p>Background</p> <p>PALB2 protein was recently identified as a partner of BRCA1 and BRCA2 which determines their proper function in DNA repair.</p> <p>Methods</p> <p>Initially, the entire coding sequence of the <it>PALB2 </it>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.</p> <p>Results</p> <p>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 <it>PALB2 </it>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 <it>PALB2 </it>mutation had also a germline nonsense mutation of the <it>BRCA2 </it>gene.</p> <p>Conclusions</p> <p>The c.509_510delGA is a novel <it>PALB2 </it>mutation that increases the risk of familial breast cancer. Occurrence of the same <it>PALB2 </it>alteration in seven unrelated women suggests that c.509_510delGA (p.R170fs) is a recurrent mutation for Polish population.</p>