Identification of a characteristic copy number alteration profile by high‐resolution single nucleotide polymorphism arrays associated with metastatic sporadic colorectal cancer

• Published in: Cancer 2014-07, Vol.120 (13), p.1948-1959
• Main Authors: González‐González, María, Fontanillo, Celia, Abad, María M., Gutiérrez, María L., Mota, Ines, Bengoechea, Oscar, Santos‐Briz, Ángel, Blanco, Oscar, Fonseca, Emilio, Ciudad, Juana, Fuentes, Manuel, Rivas, Javier, Alcazar, José A., García, Jacinto, Muñoz‐Bellvis, Luís, Orfao, Alberto, Sayagués, José M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy, Adjuvant; Chromosome Aberrations; colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; copy number change; DNA Copy Number Variations; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; In Situ Hybridization, Fluorescence; liver metastases; Liver Neoplasms - secondary; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Proteins - genetics; Neoplasm Staging; Polymorphism, Single Nucleotide; single nucleotide polymorphism array; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28681

BACKGROUND Metastatic dissemination is the most frequent cause of death in patients with sporadic colorectal cancer (sCRC). It is believed that the metastatic process is related at least in part to a specific background of genetic alterations accumulated in cells from primary tumors, and the ability to detect such alterations is critical for the identification of patients with sCRC who are at risk of developing metastases. METHODS The authors used high‐resolution, 500‐K single nucleotide polymorphism arrays to identify copy number alteration profiles present at diagnosis in primary tumors from patients with metastatic (n = 23) versus nonmetastatic (n = 26) sCRC. RESULTS The results revealed a characteristic pattern of copy number alterations in metastatic sCRC tumors that involved losses of 23 regions at chromosomes 1p, 17p, and 18q, together with gains of 35 regions at chromosomes 7 and 13q. CONCLUSIONS In line with expectations, the copy number profile investigated involved multiple genes that were associated previously with sCRC (ie, SMAD2) and/or the metastatic process (ie, podocalyxin‐like [PODXL]), and it also was associated with a poorer outcome. Cancer 2014;120:1948–1959. © 2014 American Cancer Society. The authors use high‐resolution single nucleotide polymorphism arrays to identify a characteristic copy number alteration profile at diagnosis that involves losses of chromosomes 1p, 17p, and 18q together with gains of chromosomes 7 and 13 among patients with metastatic versus nonmetastatic primary sporadic colorectal cancer. This copy number profile also is associated with poorer patient outcomes, and the involved chromosomal regions harbor specific genes associated with colorectal cancer and/or the metastatic process.