Pediatric Hematology and Oncology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
Department of Human Genetics, Hannover Medical School, Hannover, Germany.
J Hematol Oncol. 2022 Aug 16;15(1):107. doi: 10.1186/s13045-022-01332-1.
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype-phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype-phenotype correlations encouraging further analyses.
李-佛美尼综合征（Li-Fraumeni syndrome，LFS）是一种由致病性 TP53 变异引起的癌症易感性综合征。由于其频率和高癌症风险，该病症是儿童和成人中最重要的遗传致癌原因之一。Li-Fraumeni 谱这一术语反映了该病症表型可变性的演变。在此谱中，符合特定 LFS 标准的患者被诊断为 LFS，而不符合这些标准的患者则被诊断为 LFS 衰减型。为了探讨基因型-表型相关性，我们分析了在德国癌症易感性综合征登记处登记的 94 个携带有致病性 TP53 变异的家庭中的 141 名个体。21 个（22%）家庭为 LFS 衰减型，73 个（78%）家庭符合 LFS 标准。在符合 LFS 标准的家庭中，32 个（44%）存在 NULL 变异，在符合 LFS 衰减型标准的家庭中，2 个（9.5%）存在 NULL 变异（P 值<0.01）。在没有儿童癌症（除肾上腺皮质癌外）的 53 个家庭中，有 10 个存在部分功能 Kato 变异，而在除了儿童癌症（除肾上腺皮质癌外）之外的 41 个家庭中，没有一个存在这种变异（P 值<0.01）。我们的研究表明，基因型-表型相关性存在，鼓励进一步分析。
