MIR605 rs2043556 is associated with the occurrence of multiple primary tumors in TP53 p.(Arg337His) mutation carriers.

Autor: Bandeira IC; Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil., Vieira IA; Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: igvieira@hcpa.edu.br., Andreis TF; Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil., Brussa Reis L; Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil., Macedo GS; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil; Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil., Vianna FSL; Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil., Santos-Silva P; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil., Palmero EI; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Barretos School of Health Sciences, Barretos, São Paulo, Brazil., Galvão HCR; Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Ramos CRN; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Santiago KM; Oncogenetics Department, International Research Center, AC Camargo Cancer Center, National Institute of Oncogenomics, São Paulo city, São Paulo, Brazil., Achatz MI; Oncogenetics Department, International Research Center, AC Camargo Cancer Center, National Institute of Oncogenomics, São Paulo city, São Paulo, Brazil., da Costa AABA; Oncogenetics Department, International Research Center, AC Camargo Cancer Center, National Institute of Oncogenomics, São Paulo city, São Paulo, Brazil., Ashton-Prolla P; Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil; Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil; Department of Genetics, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
Jazyk: angličtina
Zdroj: Cancer genetics [Cancer Genet] 2020 Jan; Vol. 240, pp. 54-58. Date of Electronic Publication: 2019 Nov 20.
DOI: 10.1016/j.cancergen.2019.11.005
Abstrakt: Li-Fraumeni and Li-Fraumeni-like (LFS/LFL) Syndrome are cancer predisposition syndromes caused by germline pathogenic variants in TP53 and are associated with an increased risk of multiple early-onset cancers. In Southern and Southeastern Brazil, a germline founder variant with partial penetrance located in the oligomerization domain of TP53, c.1010G>A p.(Arg337His, commonly known as R337H), has been detected in 0.3% of the general population. Recently, the functional MIR605 variant rs2043556 (A>G) has been identified as a novel LFS phenotype modifier in families with germline TP53 DNA binding variants. In this study, our goal was to verify MIR605 rs2043556 allele frequencies and further explore its possible effects on the phenotype of 238 Brazilian individuals carrying TP53 p.(Arg337His). The MIR605 rs2043556 G allele was detected in 136 (57.1%) individuals, including 25 homozygotes (10.5%), and although it had been previously associated with an earlier mean age of tumor onset, this effect was not observed in this study (p = 0.8). However, in p.(Arg337His) mutation carriers, the GG genotype was significantly associated with the occurrence of multiple primary tumors (p = 0.005). We provide further evidence of MIR605 rs2043556 G allele's effect as a phenotype modulator in carriers of germline TP53 pathogenic variants.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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