Exploring the Role of the MUTYH Gene in Breast, Ovarian and Endometrial Cancer.

Autor:	Lintas C; Research Unit of Medical Genetics, Department of Medicine, University Campus-Biomedico of Rome, Via Alvaro del Portillo 21, 00128 Roma, Italy.; Operative Research Unit of Medical Genetics, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy., Canalis B; Operative Research Unit of Anatomical Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy., Azzarà A; Operative Research Unit of Medical Genetics, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy., Sabarese G; Operative Research Unit of Anatomical Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy., Perrone G; Operative Research Unit of Anatomical Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy.; Research Unit of Anatomical Pathology, Department of Medicine, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy., Gurrieri F; Research Unit of Medical Genetics, Department of Medicine, University Campus-Biomedico of Rome, Via Alvaro del Portillo 21, 00128 Roma, Italy.; Operative Research Unit of Medical Genetics, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2024 Apr 26; Vol. 15 (5). Date of Electronic Publication: 2024 Apr 26.
DOI:	10.3390/genes15050554
Abstrakt:	Background: MUTYH germline monoallelic variants have been detected in a number of patients affected by breast/ovarian cancer or endometrial cancer, suggesting a potential susceptibility role, though their significance remains elusive since the disease mechanism is normally recessive. Hence, the aim of this research was to explore the hypothesis that a second hit could have arisen in the other allele in the tumor tissue. Methods: we used Sanger sequencing and immunohistochemistry to search for a second MUTYH variant in the tumoral DNA and to assess protein expression, respectively. Results: we detected one variant of unknown significance, one variant with conflicting interpretation of pathogenicity and three benign/likely benign variants; the MUTYH protein was not detected in the tumor tissue of half of the patients, and in others, its expression was reduced. Conclusions: our results fail to demonstrate that germinal monoallelic MUTYH variants increase cancer risk through a LOH (loss of heterozygosity) mechanism in the somatic tissue; however, the absence or partial loss of the MUTYH protein in many tumors suggests its dysregulation regardless of MUTYH genetic status.
Databáze:	MEDLINE
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