Chromosomal aberrations detected by comparative genomic hybridization predict outcome in patients with colorectal carcinoma

Abstract

Abstract. To obtain comprehensive information regarding the correlation between genomic changes and clinicopathological parameters such as disease stage, metastases, and survival, we investigated genomic changes by comparative genomic hybridization (CGH) in 73 patients with colorectal cancer (CRC), and assessed the associations of such charges with clinicopathological parameters. Gains of 8q21-22, 13q21-31 and 20q12-qter and loss of 17p12-pter were detected in >50% of stage I tumors. Gain of 8q23-qter and losses of 8p12-pter and 18q12-qter were observed more frequently in stage III/IV tumors than in stage I tumors (all P<0.05). Loss of 8p12-pter and gain of 8q23-qter were linked to nodal metastasis (all P<0.05). Loss of 18q12-qter and gain of 8q23-qter were associated with distant organ metastasis at diagnosis and/or recurrence after surgery (all P<0.05). Moreover, losses of 8p12-pter and 18q12-qter and gains of 8q23 and 8q24-qter were associated significantly with unfavorable prognosis (all P<0.05). Furthermore, combined examination of the above four changes can provide a more accurate assessment for patient's prognosis. Specifically, 11 of 19 patients with these four changes died, but only 1 of 21 cases without these four changes died during the follow-up period (P<0.0001). Multivariate analysis revealed that loss of 18q12-qter is an independent prognostic marker (P=0.031). Our findings indicate that genetic aberrations detected by CGH may predict outcome in patients with CRC.

Identification of DNA copy number aberrations associated with metastases of colorectal cancer using array CGH profiles

“…The 20q gain and 18q loss that were the most frequent gain and loss, respectively in this study were also frequently detected in other studies of colorectal cancers [11][12][13][14][15]. In addition, gains of 7p, 8q and chromosome 13, and losses of 8p and 17p were shown by other investigators who examined Japanese specimens as well as by the present study [15][16][17]. These observations indicate the reliability of the present a CGH data.…”

Somatic gene copy number alterations in colorectal cancer: new quest for cancer drivers and biomarkers

“…82 The PHLPP1 (PH domain leucine-rich repeats proteinphosphatase 1) gene in 18q21.33 has been found to suppress colorectal carcinogenesis by blocking the Akt signaling pathway, and it encodes a potential cancer biomarker. 83,84 In addition, the deletions of different subregions on 18q may associate with poor outcomes in CRC, 13 including 18q12-qter reported by Liu et al, 85 and 18q12.2 (harboring the BRUNOL4 gene) revealed by Poulogiannis et al 86 The 18q12.2 segment also includes MAPRE2 (microtubule-associated protein RP/EB family member 2), ZNF24 (zinc-finger protein 24) and PIK3C3 (phosphatidylinositol3-kinase catalytic subunit type 3) that are associated with CRC development or metastasis. 30 It was examined that loss of DNAM-1 (DNAX accessory molecule 1), SOCS6 (suppressor of cytokine signaling 6) and ACHR-7 (a-7 nictonic receptor) in 18q22 associate with poor outcome in CRC.…”

Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

“…Indeed, amplifications of the 20q12 region have also been found by CGH analysis in colorectal carcinomas. 31 The role of upregulated eIF6 in ovarian serous adenocarcinoma may be interpreted as a consequence of increased protein turnover in rapidly proliferating malignant cells based on its role in ribosome assembly.…”