title: Association between genetic subgroups of pancreatic ductal adenocarcinoma defined by high density 500 K SNP-arrays and tumor histopathology.
abstract: The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP)-arrays to define those chromosomal regions which most commonly harbour copy number (CN) alterations and loss of heterozygozity (LOH) in a series of 20 PDAC tumors and we correlated the corresponding genetic profiles with the most relevant clinical and histopathological features of the disease. Overall our results showed that primary PDAC frequently display (>70%) extensive gains of chromosomes 1q, 7q, 8q and 20q, together with losses of chromosomes 1p, 9p, 12q, 17p and 18q, such chromosomal regions harboring multiple cancer- and PDAC-associated genes. Interestingly, these alterations clustered into two distinct genetic profiles characterized by gains of the 2q14.2, 3q22.1, 5q32, 10q26.13, 10q26.3, 11q13.1, 11q13.3, 11q13.4, 16q24.1, 16q24.3, 22q13.1, 22q13.31 and 22q13.32 chromosomal regions (group 1; n = 9) versus gains at 1q21.1 and losses of the 1p36.11, 6q25.2, 9p22.1, 9p24.3, 17p13.3 and Xp22.33 chromosomal regions (group 2; n = 11). From the clinical and histopathological point of view, group 1 cases were associated with smaller and well/moderately-differentiated grade I/II PDAC tumors, whereas and group 2 PDAC displayed a larger size and they mainly consisted of poorly-differentiated grade III carcinomas. These findings confirm the cytogenetic complexity and heterozygozity of PDAC and provide evidence for the association between tumor cytogenetics and its histopathological features. In addition, we also show that the altered regions identified harbor multiple cancer associate genes that deserve further investigation to determine their relevance in the pathogenesis of PDAC.
authors.affiliation: Servicio General de Citometría, Departamento de Medicina and Centro de Investigación del Cáncer (IBMCC-CSIC/USAL), Universidad de Salamanca, Salamanca, Spain.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Gutiérrez
authors.forename: Luís
authors.initials: L
authors.lastname: Muñoz-Bellvis
authors.forename: María del Mar
authors.initials: Mdel M
authors.lastname: Abad
authors.forename: Oscar
authors.initials: O
authors.lastname: Bengoechea
authors.forename: María
authors.initials: M
authors.lastname: González-González
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: José María
authors.initials: JM
authors.lastname: Sayagués
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D003582:Cytogenetics; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*