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
DOI/URL:
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Liying Zhang
    89 Zhang
  2. Eileen O'Reilly
    321 O'Reilly
  3. Michael Francis Walsh
    49 Walsh
  4. Ciyu   Yang
    8 Yang
  5. Sowmya Jairam
    6 Jairam
  6. Ozge Birsoy
    10 Birsoy