Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine and Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; email:
Boston University School of Medicine, Boston, Massachusetts, USA.
Annu Rev Genomics Hum Genet. 2022 Aug 31;23:331-361. doi: 10.1146/annurev-genom-120121-105450.
A mosaic state arises when pathogenic variants are acquired in certain cell lineages during postzygotic development, and mosaic individuals may present with a generalized or localized phenotype. Here, we review the current state of knowledge regarding mosaicism for eight common tumor suppressor genes-, , , , , , , and -and their related genetic syndromes/entities. We compare and discuss approaches for comprehensive diagnostic genetic testing, the spectrum of variant allele frequency, and disease severity. We also review affected individuals who have no mutation identified after conventional genetic analysis, as well as genotype-phenotype correlations and transmission risk for each tumor suppressor gene in full heterozygous and mosaic patients. This review provides new insight into similarities as well as marked differences regarding the appreciation of mosaicism in these tumor suppressor syndromes.
嵌合体状态是在合子后发育过程中某些细胞谱系中获得致病性变异体时出现的，嵌合体个体可能表现出全身性或局部性表型。在这里，我们回顾了关于八种常见肿瘤抑制基因—— 、 、 、 、 、 、 和 -及其相关遗传综合征/实体的嵌合体的现有知识状态。我们比较和讨论了全面诊断遗传检测的方法、变异等位基因频率的范围以及疾病严重程度。我们还回顾了在常规遗传分析后未发现突变的受影响个体，以及每个肿瘤抑制基因在完全杂合子和嵌合体患者中的基因型-表型相关性和传播风险。这项综述深入了解了这些肿瘤抑制综合征中嵌合体的相似性和显著差异。
