DNA copy number profiling reveals different patterns of chromosomal instability within colorectal cancer according to the age of onset

被引:33
作者
Arriba, Maria [1 ]
Garcia, Juan L. [2 ,3 ]
Inglada-Perez, Lucia [4 ,5 ]
Rueda, Daniel [6 ]
Osorio, Irene [7 ]
Rodriguez, Yolanda [8 ]
Alvaro, Edurne [9 ]
Sanchez, Ricard [1 ]
Fernandez, Tamara [7 ]
Perez, Jessica [2 ,3 ]
Hernandez, Jesus M. [2 ]
Benitez, Javier [5 ,10 ]
Gonzalez-Sarmiento, Rogelio [2 ,3 ]
Urioste, Miguel [5 ,11 ]
Perea, Jose [1 ,7 ]
机构
[1] 12 Octubre Univ Hosp, Ctr Biomed Res, C Rosas Aravaca 82A,1 Dcha, E-28023 Madrid, Spain
[2] Univ Hosp Salamanca USAL, CSIC, Biomed Res Inst Salamanca IBSAL, Salamanca, Spain
[3] Univ Salamanca, CSIC, Inst Mol & Cellular Biol Canc IBMCC, E-37008 Salamanca, Spain
[4] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Hereditary Endocrine Canc Grp, Madrid, Spain
[5] Inst Hlth Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
[6] 12 Octubre Univ Hosp, Mol Biol Lab, C Rosas Aravaca 82A,1 Dcha, E-28023 Madrid, Spain
[7] 12 Octubre Univ Hosp, Dept Surg, C Rosas Aravaca 82A,1 Dcha, E-28023 Madrid, Spain
[8] 12 Octubre Univ Hosp, Dept Pathol, C Rosas Aravaca 82A,1 Dcha, E-28023 Madrid, Spain
[9] Infanta Leonor Univ Hosp, Dept Surg, Madrid, Spain
[10] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genet Grp, Madrid, Spain
[11] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Familial Canc Clin Unit, Madrid, Spain
关键词
early-onset colorectal cancer; late-onset colorectal cancer; array-based comparative genomic hybridization; MICROSATELLITE INSTABILITY; GENOMIC INSTABILITY; RECTAL-CANCER; COLON-CANCER; TUMORS; HYBRIDIZATION; PHENOTYPES; GENESIS; LOSSES; SUBSET;
D O I
10.1002/mc.22315
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Chromosomal instability resulting in copy number alterations is a hallmark of colorectal cancer (CRC). However, few studies have attempted to characterize the chromosomal changes occurring in early-onset CRC in order to compare them with those taking place within the more extensively studied late-onset CRC subset. Our aim was to characterize the genomic profiles of these two groups of colorectal tumors and to compare them to each other. Array comparative genomic hybridization profiling of 146 colorectal tumors (60 early-onset and 86 late-onset) in combination with an unsupervised analysis was used to define common and specific copy number alterations. We found a number of important differences between the chromosomal instability profiles of each age subset. Thus, losses at 1p36, 1p12, 1q21, 9p13, 14q11, 16p13, and 16p12 were significantly more frequent in younger patients, whereas gains at 7q11 and 7q22 were more frequent in older patients. Moreover, the unsupervised analysis stratified the tumors into two clusters, each one of which was enriched in patients from one of the age subsets. Our findings confirm the existence of substantial differences between the chromosomal instability profiles of the two groups which are more important from a qualitative point of view. Further studies are needed to understand the clinicopathological implications of these dissimilarities. (c) 2015 Wiley Periodicals, Inc.
引用
收藏
页码:705 / 716
页数:12
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