Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
Cancer. 2014 Apr 1;120(7):963-7. doi: 10.1002/cncr.28504. Epub 2014 Jan 10.
This study sought to determine the prevalence of PALB2 mutations in a cohort referred for diagnostic testing for hereditary breast cancer.
Sanger sequencing was used to analyze the entire coding region and flanking introns of PALB2 in anonymized DNA samples from 1479 patients. Samples were stratified into a "high-risk" group, 955 samples from individuals predicted to have a high probability of carrying a mutation in BRCA1 or BRCA2 based on their personal and family history, and a "lower-risk" group consisting of 524 samples from patients with breast cancer, but fewer risk factors for being a BRCA1 or BRCA2 mutation carrier. All patients were known to be negative for deleterious sequence mutations and large rearrangements in BRCA1 and BRCA2.
We identified 12 disease-associated PALB2 mutations among the 1479 patients (0.8%). The PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice-site mutation. The mutation prevalence for the high-risk population was 1.05% (95% CI = 0.5-1.92), whereas that for the lower-risk population was 0.38% (95% CI = 0.05-1.37). We identified 59 PALB2 variants of uncertain significance (VUS) among 57 of the 1479 patients (3.9%).
These results suggest that PALB2 mutations occur at a frequency of ~1% in patients with hereditary breast cancer.
本研究旨在确定在遗传性乳腺癌患者的诊断性检测中 PALB2 突变的流行率。
使用 Sanger 测序分析了 1479 名患者匿名 DNA 样本中 PALB2 的整个编码区和侧翼内含子。将样本分为“高危”组（955 个样本）和“低危”组（524 个样本）。“高危”组中，根据个人和家族史，预测个体携带 BRCA1 或 BRCA2 突变的可能性较高；“低危”组中，患者患有乳腺癌，但作为 BRCA1 或 BRCA2 突变携带者的风险因素较少。所有患者均已知 BRCA1 和 BRCA2 中无有害序列突变和大片段重排。
在 1479 名患者中，我们发现了 12 种与疾病相关的 PALB2 突变（0.8%）。PALB2 突变包括 8 种无义突变、3 种移码突变和 1 种剪接位点突变。高危人群的突变率为 1.05%（95%CI=0.5-1.92），低危人群的突变率为 0.38%（95%CI=0.05-1.37）。在 1479 名患者中，我们发现了 57 名患者的 59 种意义不明的 PALB2 变异体（VUS）（3.9%）。
这些结果表明，遗传性乳腺癌患者中 PALB2 突变的发生率约为 1%。
