In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 9 ( 2021-9-16), p. e0251639-
Abstract:
Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by pathogenic germline variants in the TP53 gene, characterized by a predisposition to the development of a broad spectrum of tumors at an early age. The core tumors related to LFS are bone and soft tissue sarcomas, premenopausal breast cancer, brain tumors, adrenocortical carcinomas (ACC), and leukemias. The revised Chompret criteria has been widely used to establish clinical suspicion and support TP53 germline variant testing and LFS diagnosis. Information on TP53 germline pathogenic variant (PV) prevalence when using Chompret criteria in South America and especially in Brazil is scarce. Therefore, the aim of this study was to characterize patients that fulfilled these specific criteria in southern Brazil, a region known for its high population frequency of a founder TP53 variant c.1010G 〉 A (p.Arg337His), as known as R337H. TP53 germline testing of 191 cancer-affected and independent probands with LFS phenotype identified a heterozygous pathogenic/likely pathogenic variant in 26 (13.6%) probands, both in the DNA binding domain (group A) and in the oligomerization domain (group B) of the gene. Of the 26 carriers, 18 (69.23%) were R337H heterozygotes. Median age at diagnosis of the first tumor in groups A and B differed significantly in this cohort: 22 and 2 years, respectively ( P = 0.009). The present study shows the clinical heterogeneity of LFS, highlights particularities of the R337H variant and underscores the need for larger collaborative studies to better define LFS prevalence, clinical spectrum and penetrance of different germline TP53 pathogenic variants.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0251639
DOI:
10.1371/journal.pone.0251639.g001
DOI:
10.1371/journal.pone.0251639.g002
DOI:
10.1371/journal.pone.0251639.g003
DOI:
10.1371/journal.pone.0251639.t001
DOI:
10.1371/journal.pone.0251639.t002
DOI:
10.1371/journal.pone.0251639.t003
DOI:
10.1371/journal.pone.0251639.s001
DOI:
10.1371/journal.pone.0251639.s002
DOI:
10.1371/journal.pone.0251639.s003
DOI:
10.1371/journal.pone.0251639.s004
DOI:
10.1371/journal.pone.0251639.r001
DOI:
10.1371/journal.pone.0251639.r002
DOI:
10.1371/journal.pone.0251639.r003
DOI:
10.1371/journal.pone.0251639.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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