Clinicopathological and molecular characterization of Brazilian families at risk for Lynch syndrome.

Autor: de Paula AE; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Galvão HCR; Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Bonatelli M; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Sabato C; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Fernandes GC; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Berardinelli GN; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Andrade CEM; Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Neto MC; Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Romagnolo LGC; Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Campacci N; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Scapulatempo-Neto C; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Reis RM; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal., Palmero EI; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Pele Pequeno Principe Research Institute, Curitiba, Brazil; Faculdades Pequeno Principe, Curitiba, Brazil. Electronic address: edenirip@yahoo.com.br.
Jazyk: angličtina
Zdroj: Cancer genetics [Cancer Genet] 2021 Jun; Vol. 254-255, pp. 82-91. Date of Electronic Publication: 2021 Feb 14.
DOI: 10.1016/j.cancergen.2021.02.003
Abstrakt: Lynch syndrome (LS), is the most common hereditary colorectal cancer syndrome. However, it is poorly characterized in Brazil. Therefore, we aimed to determine the spectrum of pathogenic variants in Mismatch Repair (MMR) genes and investigate the MLH1 promotor methylation role as a second hit in LS tumors. Tumor screening through microsatellite instability and immunohistochemistry for MMR proteins was performed in 323 cases who met clinical criteria. BRAF-V600E and MLH1 promoter methylation were analyzed for all MLH1-deficient tumors. Patients with MMR deficient tumor proceeded to germline genetic testing. MMR deficient tumors were detected in 41% of patients recruited. About half of patients carried a pathogenic germline variant. Two recurrent variants in MLH1 and three novel pathogenic variants were identified. Furthermore, pathogenic germline variants with concomitant somatic MLH1 hypermethylation were found in 6% of cases. Predictive genetic testing was offered to 387 relatives. Overall, 127 tumors were diagnosed in 100 LS patients, from 62 unrelated families. Our molecular data provide new information about the spectrum of MMR mutations, which contributes to a better characterization of LS in Brazil. Furthermore, we call attention to the possibility of failure in the diagnosis of germline MLH1 mutation carriers when somatic MLH1 hypermethylation is used to rule out LS.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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