A synonymous germline variant PALB2 c.18G>T (p.Gly6=) disrupts normal splicing in a family with pancreatic and breast cancers Journal Article


Authors: Yang, C.; Ceyhan-Birsoy, O.; Mandelker, D.; Jairam, S.; Catchings, A.; O’Reilly, E. M.; Walsh, M. F.; Zhang, L.
Article Title: A synonymous germline variant PALB2 c.18G>T (p.Gly6=) disrupts normal splicing in a family with pancreatic and breast cancers
Abstract: Purpose: Mutations in PALB2 have been associated with a predisposition to breast and pancreatic cancers. This study aims to characterize a novel PALB2 synonymous variant c.18G>T (p.Gly6=) identified in a family with pancreatic and breast cancers. Methods: The PALB2 c.18G>T (p.Gly6=) variant in this family was identified using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACTTM). RT-PCR and subsequent cloning were performed to investigate whether this variant affects normal splicing. Results: This variant completely disrupts normal splicing and leads to several abnormal transcripts, which presumably leads to premature protein truncation. The major abnormal transcript resulted in a deletion of 32 base pairs in exon 1 and frameshift. Conclusions: Our results indicate that the PALB2 c.18G>T (p.Gly6=) variant is likely pathogenic. This study provided important laboratory evidence for classification of this variant and guided improved patient management. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: splicing; palb2; synonymous germline variant
Journal Title: Breast Cancer Research and Treatment
Volume: 173
Issue: 1
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2019-01-01
Start Page: 79
End Page: 86
Language: English
DOI: 10.1007/s10549-018-4980-y
PROVIDER: scopus
PUBMED: 30255452
PMCID: PMC6785047
DOI/URL:
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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MSK Authors
  1. Liying Zhang
    129 Zhang
  2. Eileen O'Reilly
    783 O'Reilly
  3. Michael Francis Walsh
    156 Walsh
  4. Diana Lauren Mandelker
    178 Mandelker
  5. Ciyu   Yang
    26 Yang
  6. Sowmya Jairam
    13 Jairam
  7. Ozge Birsoy
    69 Birsoy