Insights Into the Somatic Mutation Burden of Hepatoblastomas From Brazilian Patients

Aguiar, Talita Ferreira Marques; Rivas, Maria Prates; Costa, Silvia Souza da; Maschietto, Mariana; Rodrigues, T.; Barros, Juliana Sobral de; Barbosa, Anne Caroline; Valieris, Renan; Fernandes, Gustavo Ribeiro; Bertola, Débora Romeo; Cypriano, Mônica; Toledo, Sílvia Regina Caminada de; Major, Angela; Tojal, Israel; Apezzato, Maria Lúcia de Pinho; Carraro, Dirce Maria; Rosenberg, Carla; Costa, C; Cunha, Isabela W.; Sarabia, Stephen F.; Terrada, Dolores-López; Krepischi, Ana Cristina Victorino

doi:10.3389/fonc.2020.00556

Cited by 16 publications

(25 citation statements)

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“…Different CYP1A1 variants were identified in Patients 1 (c.1390C>A) and 2 (c.877C>G), both classified as VUS; additionally, one variant was detected in the Patient 2 affecting CEP164 (c.1429C>T), somatic mutations in this gene were previously reported in HB samples 14 . The variants in the CYP1A1 and CEP164 genes were validated by Sanger sequencing (Figure 2).…”

Section: Germline Variantsmentioning

confidence: 80%

“…We also detected, in both patients, germline variants in the geneCYP1A1 . One variant in this gene was previously reported in a case of congenital hepatoblastoma 14 . CYP1A1 encodes a protein member of the cytochrome P450 superfamily of enzymes 66 ; the expression of this gene is transcriptionally regulated through the AhR receptor, which plays an important role as a mediator of the adaptive response to xenobiotics and also contributes to normal physiology and embryonic development 67 .…”

Section: Discussionmentioning

confidence: 91%

“…Particularly, variants in genesCEP164 and CYP1A1 were interesting because they were previously observed in an HB exome study of somatic mutations 14 . CEP164 encodes a protein responsible for the repair signaling when DNA damage occurs 65 .…”

Section: Discussionmentioning

confidence: 95%

“…CEP164 encodes a protein responsible for the repair signaling when DNA damage occurs 65 . This gene is involved in the stability of the genome and was previously found to be somatically mutated in two hepatoblastomas 14 . A germline variant was identified in the CEP164 of the Patient 2.…”

Section: Discussionmentioning

confidence: 99%

“…Hepatoblastoma (HB) is the most common malignant tumor of liver in the pediatric population 9 , although it is considered an ultrarare disease, accounting for only 1% of pediatric tumors 10,11 . In Brazil, collected data on hepatoblastomas are concordant with the worldwide prevalence [12][13][14] . Increased risk for hepatoblastoma development has been reported in association with specific congenital syndromes, including Beckwith-Wiedemann 15,16 , familial adenomatous polyposis (FAP) 17 , and trisomy of chromosome 18 18 .…”

Section: Introductionmentioning

confidence: 99%

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Birth Defects and Childhood Cancer: A Shared Biological Pathway for Hirschsprung Disease and Hepatoblastoma Development?

Aguiar

Teixeira

Barros

et al. 2020

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Background: The association of birth defects and developmental alterations with pediatric cancer is a recognized long-standing global observation, although very few syndromes confer a high risk of hepatoblastoma development. Procedures: Here we describe the results of germline exome analysis of two syndromic patients with Hirschsprung disease who developed hepatoblastoma. Results: Germline variants of uncertain clinical significance (VUS) were disclosed in 28 genes that might be related to patients' phenotypes. More importantly, germline VUS were detected in eight known cancer predisposition genes (APC, BRCA1, ERBB2, ERCC2, HRAS, ODC1, SERPINA6, and MCC). Additionally, our data disclosed two candidate genes with germline variants potentially contributing to the phenotype of these patients, namely, CEP164 and CYP1A1. The last one was the only gene presenting variants of uncertain significance in both patients. This gene encodes the most important xenobiotic-metabolizing enzyme of the placenta for which relevant inducible activity has been demonstrated throughout pregnancy. Conclusion: our data pointed out a set of genes that are enriched for pathways already related to cancer and developmental biology, suggesting they could have a broader role in cancer and congenital abnormalities. These results can help future studies to understand the biology of Hirschsprung disease and its association with hepatoblastoma.

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Section: Germline Variantsmentioning

confidence: 80%