Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer
Colorectal cancer (CRC) is often characterized by mutations and aberrant DNA methylation within the promoters of tumor suppressor genes and proto-oncogenes. The most frequent somatic mutations occur within KRAS and BRAF genes. Mutations of the KRAS gene have been detected in approximately 40% of pat...
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doaj-081157871d384aa89c473e62be9a16142021-07-01T17:50:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-07-011110.3389/fonc.2021.697409697409Crosstalk Between DNA Methylation and Gene Mutations in Colorectal CancerMaria Dobre0Alessandro Salvi1Iulia Andreea Pelisenco2Florina Vasilescu3Giuseppina De Petro4Vlad Herlea5Elena Milanesi6Laboratory of Histopathology and Immunohistochemistry, Victor Babes National Institute of Pathology, Bucharest, RomaniaDivision of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyFaculty of Biology, University of Bucharest, Bucharest, RomaniaLaboratory of Histopathology and Immunohistochemistry, Victor Babes National Institute of Pathology, Bucharest, RomaniaDivision of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyDepartment of Pathology, Fundeni Clinical Institute, Bucharest, RomaniaLaboratory of Radiobiology, Victor Babes National Institute of Pathology, Bucharest, RomaniaColorectal cancer (CRC) is often characterized by mutations and aberrant DNA methylation within the promoters of tumor suppressor genes and proto-oncogenes. The most frequent somatic mutations occur within KRAS and BRAF genes. Mutations of the KRAS gene have been detected in approximately 40% of patients, while mutations in BRAF have been detected less frequently at a rate of 10%. In this study, the DNA methylation levels of 22 candidate genes were evaluated in three types of tissue: mucosal tumoral tissue from 18 CRC patients, normal adjacent tissues from 10 CRC patients who underwent surgical resection, and tissue from a control group of six individuals with normal colonoscopies. A differential methylation profile of nine genes (RUNX3, SFRP1, WIF1, PCDH10, DKK2, DKK3, TMEFF2, OPCML, and SFRP2) presenting high methylation levels in tumoral compared to normal tissues was identified. KRAS mutations (codons 12 or 13) were detected in eight CRC cases, and BRAF mutations (codon 600) in four cases. One of the CRC patients presented concomitant mutations in KRAS codon 12 and BRAF, whereas seven patients did not present these mutations (WT). When comparing the methylation profile according to mutation status, we found that six genes (SFRP2, DKK2, PCDH10, TMEFF2, SFRP1, HS3ST2) showed a methylation level higher in BRAF positive cases than BRAF negative cases. The molecular sub-classification of CRC according to mutations and epigenetic modifications may help to identify epigenetic biomarkers useful in designing personalized strategies to improve patient outcomes.https://www.frontiersin.org/articles/10.3389/fonc.2021.697409/fullcolorectal cancerDNA methylationKRASBRAFmutations |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Dobre Alessandro Salvi Iulia Andreea Pelisenco Florina Vasilescu Giuseppina De Petro Vlad Herlea Elena Milanesi |
spellingShingle |
Maria Dobre Alessandro Salvi Iulia Andreea Pelisenco Florina Vasilescu Giuseppina De Petro Vlad Herlea Elena Milanesi Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer Frontiers in Oncology colorectal cancer DNA methylation KRAS BRAF mutations |
author_facet |
Maria Dobre Alessandro Salvi Iulia Andreea Pelisenco Florina Vasilescu Giuseppina De Petro Vlad Herlea Elena Milanesi |
author_sort |
Maria Dobre |
title |
Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer |
title_short |
Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer |
title_full |
Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer |
title_fullStr |
Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer |
title_full_unstemmed |
Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer |
title_sort |
crosstalk between dna methylation and gene mutations in colorectal cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-07-01 |
description |
Colorectal cancer (CRC) is often characterized by mutations and aberrant DNA methylation within the promoters of tumor suppressor genes and proto-oncogenes. The most frequent somatic mutations occur within KRAS and BRAF genes. Mutations of the KRAS gene have been detected in approximately 40% of patients, while mutations in BRAF have been detected less frequently at a rate of 10%. In this study, the DNA methylation levels of 22 candidate genes were evaluated in three types of tissue: mucosal tumoral tissue from 18 CRC patients, normal adjacent tissues from 10 CRC patients who underwent surgical resection, and tissue from a control group of six individuals with normal colonoscopies. A differential methylation profile of nine genes (RUNX3, SFRP1, WIF1, PCDH10, DKK2, DKK3, TMEFF2, OPCML, and SFRP2) presenting high methylation levels in tumoral compared to normal tissues was identified. KRAS mutations (codons 12 or 13) were detected in eight CRC cases, and BRAF mutations (codon 600) in four cases. One of the CRC patients presented concomitant mutations in KRAS codon 12 and BRAF, whereas seven patients did not present these mutations (WT). When comparing the methylation profile according to mutation status, we found that six genes (SFRP2, DKK2, PCDH10, TMEFF2, SFRP1, HS3ST2) showed a methylation level higher in BRAF positive cases than BRAF negative cases. The molecular sub-classification of CRC according to mutations and epigenetic modifications may help to identify epigenetic biomarkers useful in designing personalized strategies to improve patient outcomes. |
topic |
colorectal cancer DNA methylation KRAS BRAF mutations |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.697409/full |
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