Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility Journal Article

Authors: Pinto, E. M.; Fridman, C.; Figueiredo, B. C.; Salvador, H.; Teixeira, M. R.; Pinto, C.; Pinheiro, M.; Kratz, C. P.; Lavarino, C.; Legal, E. A. M. F.; Le, A.; Kelly, G.; Koeppe, E.; Stoffel, E. M.; Breen, K.; Hahner, S.; Heinze, B.; Techavichit, P.; Krause, A.; Ogata, T.; Fujisawa, Y.; Walsh, M. F.; Rana, H. Q.; Maxwell, K. N.; Garber, J. E.; Rodriguez-Galindo, C.; Ribeiro, R. C.; Zambetti, G. P.
Article Title: Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility
Abstract: The germline TP53 p.R337H mutation is reported as the most common germline TP53 variant. It exists at a remarkably high frequency in the population of southeast Brazil as founder mutation in two distinct haplotypes with the most frequent co-segregating with the p.E134∗ variant of the XAF1 tumor suppressor and an increased cancer risk. Founder mutations demonstrate linkage disequilibrium with neighboring genetic polymorphic markers that can be used to identify the founder variant in different geographic regions and diverse populations. We report here a shared haplotype among Brazilian, Portuguese, and Spanish families and the existence of three additional distinct TP53 p.R337H alleles. Mitochondrial DNA sequencing and Y-STR profiling of Brazilian carriers of the founder TP53 p.R337H allele reveal an excess of Native American haplogroups in maternal lineages and exclusively European haplogroups in paternal lineages, consistent with communities established through male European settlers with extensive intermarriage with Indigenous women. The identification of founder and independent TP53 p.R337H alleles underlines the importance for considering the haplotype as a functional unit and the additive effects of constitutive polymorphisms and associated variants in modifier genes that can influence the cancer phenotype. © 2023 The Author(s)
Keywords: haplotype; brazil; mitochondrial dna; cancer predisposition; founder mutation; ancestry; r337h; iberian peninsula; sephardic jewish; y-str
Journal Title: Human Genetics and Genomics Advances
Volume: 5
Issue: 1
ISSN: 2666-2477
Publisher: Cell Press  
Date Published: 2024-01-11
Start Page: 100244
Language: English
DOI: 10.1016/j.xhgg.2023.100244
PUBMED: 37794678
PROVIDER: scopus
PMCID: PMC10597792
Notes: Article -- Source: Scopus
Citation Impact
MSK Authors
  1. Michael Francis Walsh
    139 Walsh
  2. Kelsey E Breen
    17 Breen