A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer
8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417301652 |
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| author | Alessandra Viel Alessandro Bruselles Ettore Meccia Mara Fornasarig Michele Quaia Vincenzo Canzonieri Eleonora Policicchio Emanuele Damiano Urso Marco Agostini Maurizio Genuardi Emanuela Lucci-Cordisco Tiziana Venesio Aline Martayan Maria Grazia Diodoro Lupe Sanchez-Mete Vittoria Stigliano Filomena Mazzei Francesca Grasso Alessandro Giuliani Marta Baiocchi Roberta Maestro Giuseppe Giannini Marco Tartaglia Ludmil B. Alexandrov Margherita Bignami |
| author_facet | Alessandra Viel Alessandro Bruselles Ettore Meccia Mara Fornasarig Michele Quaia Vincenzo Canzonieri Eleonora Policicchio Emanuele Damiano Urso Marco Agostini Maurizio Genuardi Emanuela Lucci-Cordisco Tiziana Venesio Aline Martayan Maria Grazia Diodoro Lupe Sanchez-Mete Vittoria Stigliano Filomena Mazzei Francesca Grasso Alessandro Giuliani Marta Baiocchi Roberta Maestro Giuseppe Giannini Marco Tartaglia Ludmil B. Alexandrov Margherita Bignami |
| author_sort | Alessandra Viel |
| collection | DOAJ |
| description | 8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome. Here, we perform whole-exome sequencing that reveals a modest mutator phenotype in MAP CRCs compared to sporadic CRC stem cell lines or bulk tumours. The excess G:C>T:A transversion mutations in MAP CRCs exhibits a novel mutational signature, termed Signature 36, with a strong sequence dependence. The MUTYH mutational signature reflecting persistent 8-oxoG:A mismatches occurs frequently in the APC, KRAS, PIK3CA, FAT4, TP53, FAT1, AMER1, KDM6A, SMAD4 and SMAD2 genes that are associated with CRC. The occurrence of Signature 36 in other types of human cancer indicates that DNA 8-oxoguanine-related mutations might contribute to the development of cancer in other organs. |
| first_indexed | 2024-12-11T11:45:55Z |
| format | Article |
| id | doaj.art-87411eb9092b40f79ab724c1640e5e09 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T11:45:55Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-87411eb9092b40f79ab724c1640e5e092022-12-22T01:08:29ZengElsevierEBioMedicine2352-39642017-06-0120C394910.1016/j.ebiom.2017.04.022A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal CancerAlessandra Viel0Alessandro Bruselles1Ettore Meccia2Mara Fornasarig3Michele Quaia4Vincenzo Canzonieri5Eleonora Policicchio6Emanuele Damiano Urso7Marco Agostini8Maurizio Genuardi9Emanuela Lucci-Cordisco10Tiziana Venesio11Aline Martayan12Maria Grazia Diodoro13Lupe Sanchez-Mete14Vittoria Stigliano15Filomena Mazzei16Francesca Grasso17Alessandro Giuliani18Marta Baiocchi19Roberta Maestro20Giuseppe Giannini21Marco Tartaglia22Ludmil B. Alexandrov23Margherita Bignami24Functional Onco-Genomics and Genetics, CRO Aviano National Cancer Institute, Aviano, ItalyDepartment of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, ItalyDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, ItalyUnit of Gastroenterology, CRO Aviano National Cancer Institute, Aviano, ItalyFunctional Onco-Genomics and Genetics, CRO Aviano National Cancer Institute, Aviano, ItalyUnit of Pathology, CRO Aviano National Cancer Institute, Aviano, ItalyGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, ItalyFirst Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, ItalyFirst Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, ItalyInstitute of Genomic Medicine, Catholic University, Rome, ItalyInstitute of Genomic Medicine, Catholic University, Rome, ItalyUnit of Pathology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Turin, ItalyDivision of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, Rome, ItalyDivision of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, Rome, ItalyDivision of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, Rome, ItalyDivision of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, Rome, ItalyDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, ItalyDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, ItalyDepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, ItalyDepartment of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, ItalyFunctional Onco-Genomics and Genetics, CRO Aviano National Cancer Institute, Aviano, ItalyDepartment of Molecular Medicine, University La Sapienza, Rome, ItalyGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, ItalyTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USADepartment of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome. Here, we perform whole-exome sequencing that reveals a modest mutator phenotype in MAP CRCs compared to sporadic CRC stem cell lines or bulk tumours. The excess G:C>T:A transversion mutations in MAP CRCs exhibits a novel mutational signature, termed Signature 36, with a strong sequence dependence. The MUTYH mutational signature reflecting persistent 8-oxoG:A mismatches occurs frequently in the APC, KRAS, PIK3CA, FAT4, TP53, FAT1, AMER1, KDM6A, SMAD4 and SMAD2 genes that are associated with CRC. The occurrence of Signature 36 in other types of human cancer indicates that DNA 8-oxoguanine-related mutations might contribute to the development of cancer in other organs.http://www.sciencedirect.com/science/article/pii/S2352396417301652MUTYH-associated polyposisColorectal cancer8-OxoguanineBase excision repairExome sequencingMutational signature |
| spellingShingle | Alessandra Viel Alessandro Bruselles Ettore Meccia Mara Fornasarig Michele Quaia Vincenzo Canzonieri Eleonora Policicchio Emanuele Damiano Urso Marco Agostini Maurizio Genuardi Emanuela Lucci-Cordisco Tiziana Venesio Aline Martayan Maria Grazia Diodoro Lupe Sanchez-Mete Vittoria Stigliano Filomena Mazzei Francesca Grasso Alessandro Giuliani Marta Baiocchi Roberta Maestro Giuseppe Giannini Marco Tartaglia Ludmil B. Alexandrov Margherita Bignami A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer EBioMedicine MUTYH-associated polyposis Colorectal cancer 8-Oxoguanine Base excision repair Exome sequencing Mutational signature |
| title | A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer |
| title_full | A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer |
| title_fullStr | A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer |
| title_full_unstemmed | A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer |
| title_short | A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer |
| title_sort | specific mutational signature associated with dna 8 oxoguanine persistence in mutyh defective colorectal cancer |
| topic | MUTYH-associated polyposis Colorectal cancer 8-Oxoguanine Base excision repair Exome sequencing Mutational signature |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417301652 |
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