title: Unsupervised Analysis of Array Comparative Genomic Hybridization Data from Early-Onset Colorectal Cancer Reveals Equivalence with Molecular Classification and Phenotypes.
abstract: To investigate whether chromosomal instability (CIN) is associated with tumor phenotypes and/or with global genomic status based on MSI (microsatellite instability) and CIMP (CpG island methylator phenotype) in early-onset colorectal cancer (EOCRC).
  
  
  
  Taking as a starting point our previous work in which tumors from 60 EOCRC cases (≤45 years at the time of diagnosis) were analyzed by array comparative genomic hybridization (aCGH), in the present study we performed an unsupervised hierarchical clustering analysis of those aCGH data in order to unveil possible associations between the CIN profile and the clinical features of the tumors. In addition, we evaluated the MSI and the CIMP statuses of the samples with the aim of investigating a possible relationship between copy number alterations (CNAs) and the MSI/CIMP condition in EOCRC.
  
  
  
  Based on the similarity of the CNAs detected, the unsupervised analysis stratified samples into two main clusters (A, B) and four secondary clusters (A1, A2, B3, B4). The different subgroups showed a certain correspondence with the molecular classification of colorectal cancer (CRC), which enabled us to outline an algorithm to categorize tumors according to their CIMP status. Interestingly, each subcluster showed some distinctive clinicopathological features. But more interestingly, the CIN of each subcluster mainly affected particular chromosomes, allowing us to define chromosomal regions more specifically affected depending on the CIMP/MSI status of the samples.
  
  
  
  Our findings may provide a basis for a new form of classifying EOCRC according to the genomic status of the tumors.
authors.affiliation: Centre for Biomedical Research of the 12 de Octubre University Hospital, Avda. de Córdoba, S/N, 28041, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Arriba
authors.affiliation: Biomedical Research Institute of Salamanca (IBSAL). University Hospital of Salamanca-USAL-CSIC, P° de San Vicente, 58-182, 37007, Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
authors.forename: Juan L
authors.initials: JL
authors.lastname: García
authors.affiliation: Molecular Biology Laboratory, 12 de Octubre University Hospital, Avda. de Córdoba, S/N, 28041, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rueda
authors.affiliation: Biomedical Research Institute of Salamanca (IBSAL). University Hospital of Salamanca-USAL-CSIC, P° de San Vicente, 58-182, 37007, Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Pérez
authors.affiliation: Department of Surgery, 12 de Octubre University Hospital. Avda. de Córdoba, S/N, 28041, Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Brandariz
authors.affiliation: Department of Surgery, 12 de Octubre University Hospital. Avda. de Córdoba, S/N, 28041, Madrid, Spain.
authors.forename: Oana A
authors.initials: OA
authors.lastname: Nutu
authors.affiliation: Department of Surgery, 12 de Octubre University Hospital. Avda. de Córdoba, S/N, 28041, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Alonso
authors.affiliation: Department of Pathology, 12 de Octubre University Hospital, Avda. de Córdoba, S/N, 28041, Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Rodríguez
authors.affiliation: Familial Cancer Clinical Unit, Human Cancer Genetics Program. Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Urioste
authors.affiliation: Biomedical Research Institute of Salamanca (IBSAL). University Hospital of Salamanca-USAL-CSIC, P° de San Vicente, 58-182, 37007, Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.affiliation: Centre for Biomedical Research of the 12 de Octubre University Hospital, Avda. de Córdoba, S/N, 28041, Madrid, Spain; Department of Surgery, 12 de Octubre University Hospital. Avda. de Córdoba, S/N, 28041, Madrid, Spain. Electronic address: josepereag@hotmail.com.
authors.forename: José
authors.initials: J
authors.lastname: Perea
mesh_terms: D000293:Adolescent; D000328:Adult; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D055028:Comparative Genomic Hybridization; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010641:Phenotype; D011401:Promoter Regions, Genetic; D055815:Young Adult