Type and frequency of MUTYH variants in Italian patients with suspected MAP: a retrospective multicenter study.
To determine prevalence, spectrum and genotype-phenotype correlations of MUTYH variants in Italian patients with suspected MAP (MUTYH-associated polyposis), a retrospective analysis was conducted to identify patients who had undergone MUTYH genetic testing from September 2002 to February 2014. Results of genetic testing and patient clinical characteristics were collected (gender, number of polyps, age at polyp diagnosis, presence of colorectal cancer (CRC) and/or other cancers, family data). The presence of large rearrangements of the MUTYH gene was evaluated by Multiplex Ligation-dependent Probe Amplification analysis. In all, 299 patients with colorectal neoplasia were evaluated: 61.2% were males, the median age at polyps or cancer diagnosis was 50 years (16-80 years), 65.2% had <100 polyps and 51.8% had CRC. A total of 36 different MUTYH variants were identified: 13 (36.1%) were classified as pathogenetic, whereas 23 (63.9%) were variants of unknown significance (VUS). Two pathogenetic variants were observed in 78 patients (26.1%). A large homozygous deletion of exon 15 was found in one patient (<1.0%). MAP patients were younger than those with negative MUTYH testing at polyps diagnosis (P<0.0001) and at first cancer diagnosis (P=0.007). MAP patients carrying the p.Glu480del variant presented with a younger age at polyp diagnosis as compared to patients carrying p.Gly396Asp and p.Tyr179Cys variants. A high heterogeneity of MUTYH variants and a high rate of VUS were identified in a cohort of Italian patients with suspected MAP. Genotype-phenotype analysis suggests that the p.Glu480del variant is associated with a severe phenotype.
Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy.
Maria Teresa
MT
Ricci
Research Center on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Sara
S
Miccoli
Research Center on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Daniela
D
Turchetti
Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy.
Davide
D
Bondavalli
Funcional Onco-genomics and Genetics, CRO Aviano National Cancer Institute, Aviano (PN), Italy.
Alessandra
http://orcid.org/0000-0003-2804-0840
A
Viel
Funcional Onco-genomics and Genetics, CRO Aviano National Cancer Institute, Aviano (PN), Italy.
Michele
M
Quaia
Funcional Onco-genomics and Genetics, CRO Aviano National Cancer Institute, Aviano (PN), Italy.
Elisa
E
Giacomini
Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy.
Viviana
V
Gismondi
Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute-IRCCS, Rome, Italy.
Lupe
L
Sanchez-Mete
Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute-IRCCS, Rome, Italy.
Vittoria
V
Stigliano
Clinical Pathology Unit, Regina Elena National Cancer Institute-IRCCS, Rome, Italy.
Aline
A
Martayan
Unit of Experimental and Computational Carcinogenesis, Istituto Superiore di Sanità, Rome, Italy.
Filomena
F
Mazzei
Unit of Experimental and Computational Carcinogenesis, Istituto Superiore di Sanità, Rome, Italy.
Margherita
M
Bignami
Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genoa, Italy.
Luigina
L
Bonelli
Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy.
Liliana
http://orcid.org/0000-0003-4871-6668
L
Varesco
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003111:Colonic Polyps / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D055815:Young Adult
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase