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18.10.2016 | Preclinical study

Characterization of a novel germline PALB2 duplication in a hereditary breast and ovarian cancer family

verfasst von: Ciyu Yang, Angela G. Arnold, Magan Trottier, Yukio Sonoda, Nadeem R. Abu-Rustum, Oliver Zivanovic, Mark E. Robson, Zsofia K. Stadler, Michael F. Walsh, David M. Hyman, Kenneth Offit, Liying Zhang

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2016

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Abstract

Purpose

Mutations in PALB2 have been associated with a predisposition to breast and pancreatic cancers. This study aims to characterize a novel PALB2 exon 13 duplication in a hereditary breast and ovarian cancer family.

Methods

The PALB2 exon 13 duplication in this family was evaluated using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT™) and confirmed by multiplex ligation-dependent probe amplification (MLPA). The duplication breakpoints were determined by long-range PCR and DNA sequencing. The effects of this mutation on mRNA splicing were characterized using RT-PCR, cloning, and DNA sequencing.

Results

The 5′ and 3′ breakpoints were mapped to intron 12 and downstream of 3′UTR. The tandem duplication is mediated by Alu elements in these regions. This duplication disrupts normal mRNA splicing and presumably leads to a frameshift and premature protein truncation. This duplication segregates with ovarian and breast cancer in multiple members in this family.

Conclusions

Our results indicate that the PALB2 exon 13 duplication is a pathogenic variant. The presence of the PALB2 duplication in the proband affected with high-grade serous ovarian cancer suggests that PALB2 might be associated with a predisposition to ovarian cancer.

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Titel: Characterization of a novel germline PALB2 duplication in a hereditary breast and ovarian cancer family
verfasst von: Ciyu Yang
Angela G. Arnold
Magan Trottier
Yukio Sonoda
Nadeem R. Abu-Rustum
Oliver Zivanovic
Mark E. Robson
Zsofia K. Stadler
Michael F. Walsh
David M. Hyman
Kenneth Offit
Liying Zhang
Publikationsdatum: 18.10.2016
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2016
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-016-4021-7

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Springer Medizin

Characterization of a novel germline PALB2 duplication in a hereditary breast and ovarian cancer family

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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