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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2010

Open Access 01-12-2010 | Research article

A novel germline PALB2 deletion in Polish breast and ovarian cancer patients

Authors: Agnieszka Dansonka-Mieszkowska, Anna Kluska, Joanna Moes, Michalina Dabrowska, Dorota Nowakowska, Anna Niwinska, Pawel Derlatka, Krzysztof Cendrowski, Jolanta Kupryjanczyk

Published in: BMC Medical Genetics | Issue 1/2010

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Abstract

Background

PALB2 protein was recently identified as a partner of BRCA1 and BRCA2 which determines their proper function in DNA repair.

Methods

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.

Results

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.

Conclusions

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.
Appendix
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Metadata
Title
A novel germline PALB2 deletion in Polish breast and ovarian cancer patients
Authors
Agnieszka Dansonka-Mieszkowska
Anna Kluska
Joanna Moes
Michalina Dabrowska
Dorota Nowakowska
Anna Niwinska
Pawel Derlatka
Krzysztof Cendrowski
Jolanta Kupryjanczyk
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2010
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-11-20

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