Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Departments of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Breast Cancer Res Treat. 2019 Jan;173(1):79-86. doi: 10.1007/s10549-018-4980-y. Epub 2018 Sep 25.
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.
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-IMPACT™). RT-PCR and subsequent cloning were performed to investigate whether this variant affects normal splicing.
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.
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.
PALB2 中的突变与乳腺癌和胰腺癌的易感性有关。本研究旨在描述一个在具有胰腺癌和乳腺癌家族中发现的新型 PALB2 同义变体 c.18G>T（p.Gly6=）。
使用纪念斯隆凯特琳综合行动癌症靶标突变分析（MSK-IMPACT™）鉴定该家族中的 PALB2 c.18G>T（p.Gly6=）变体。进行 RT-PCR 及随后的克隆以研究该变体是否影响正常剪接。
该变体完全破坏了正常剪接，并导致几种异常转录本，推测这导致了过早的蛋白质截断。主要的异常转录本导致外显子 1 中的 32 个碱基缺失和移码。
我们的结果表明，PALB2 c.18G>T（p.Gly6=）变体很可能是致病性的。本研究为该变体的分类提供了重要的实验室证据，并指导了患者管理的改进。
