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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