title: Unexpected frequency of genomic alterations in histologically normal colonic tissue from colon cancer patients.
abstract: As shown by genomic studies, colorectal cancer (CRC) is a highly heterogeneous disease, where copy number alterations (CNAs) may greatly vary among different patients. To explore whether CNAs may be present also in histologically normal tissues from patients affected by CRC, we performed CGH + SNP Microarray on 15 paired tumoral and normal samples. Here, we report for the first time the occurrence of CNAs as a common feature of the histologically normal tissue from CRC patients, particularly CNAs affecting different oncogenes and tumor-suppressor genes, including some not previously reported in CRC and others known as being involved in tumor progression. Moreover, from the comparison of normal vs paired tumoral tissue, we were able to identify three groups: samples with an increased number of CNAs in tumoral vs normal tissue, samples with a similar number of CNAs in both tissues, and samples with a decrease of CNAs in tumoral vs normal tissue, which may be likely due to a selection of the cell population within the tumor. In conclusion, our approach allowed us to uncover for the first time an unexpected frequency of genetic alteration in normal tissue, suggesting that tumorigenic genetic lesions are already present in histologically normal colonic tissue and that the use in array comparative genomic hybridization (CGH) studies of normal samples as reference for the paired tumors can lead to misrepresented genomic data, which may be incomplete or limited, especially if used for the research of target molecules for personalized therapy and for the possible correlation with clinical outcome.
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy. donatella.conconi@unimib.it.
authors.forename: Donatella
authors.identifier: http://orcid.org/0000-0001-5665-9558
authors.initials: D
authors.lastname: Conconi
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Redaelli
authors.affiliation: Unit of Pathology, San Gerardo Hospital, Monza, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bovo
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.|Section of Pathology, Desio Hospital, Desio, Italy.
authors.forename: Biagio Eugenio
authors.initials: BE
authors.lastname: Leone
authors.affiliation: Department of Pathology, Valduce Hospital, Como, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Filippi
authors.affiliation: Department of Pathology, Valduce Hospital, Como, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Ambrosiani
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cerrito
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Grassilli
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giovannoni
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.|Medical Genetics Laboratory, San Gerardo Hospital, Monza, Italy.
authors.forename: Leda
authors.initials: L
authors.lastname: Dalprà
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Lavitrano
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002869:Chromosome Aberrations; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: Colorectal cancer; Copy number alterations; Histologically normal tissue; Precancerous conditions