A genome‐wide study of the relationship between chromosomal abnormalities and gene expression in colorectal tumors

Abstract

The role of somatic copy number alterations (SCNAs) that occur in colorectal tumors is poorly understood. SCNAs are correlated with corresponding gene expression changes that may contribute to neoplastic progression. Thus, we examined SCNAs and the expression of messenger RNAs (mRNAs) located at corresponding loci in colorectal neoplasia, a progression model of human neoplasm. We used 42 colorectal neoplastic samples, including adenomas, intramucosal cancers (IMC) and invasive colorectal cancers (CRC) that were microsatellite stable (MSS) using a genome‐wide SNP array and gene expression array (first cohort). In addition, validation analyses were examined (37 colorectal neoplasias). None of the mRNAs with a corresponding SCNA was found in the adenomas. However, three mRNAs, including ARFGEF2 at 20q13.13, N4BP2L2 at 13q13.1 and OLFM4 at 13q14.3 with a copy number (CN) gain at the corresponding locus were upregulated in IMCs of the first cohort. Moreover, upregulated expression of ARFGEF2 and OLFM4 was upregulated in the validation analysis. Finally, 28 mRNAs with gains of corresponding loci were pooled in invasive CRC of the first cohort. The mRNAs, including ACSS2 (20q11.22), DDX27 (20q13.13), MAPRE1 (20q11.21), OSBPL2 (20q11.22) and PHF20 (20q11.22‐q11.23) with CN gains of the corresponding loci were identified in 28 mRNAs. Four of these mRNAs (DDX27, MAPRE1, OSBPL2 and PHF20) were upregulated in the invasive CRC in the validation analysis. We conclude that specific 13q and 22q CN gains with gene expression changes in the corresponding loci may play an important role in IMC cells' progression into invasive CRC.

A genome‐wide analysis of the molecular alterations occurring in the adenomatous and carcinomatous components of the same tumor based on the adenoma–carcinoma sequence

“…However, none of the genes corresponding to these gains showed altered expression. This finding suggests that although CN gains at 20q11.21–q13.33, 8q13.3, 8p23.1, or 8q21.2–q22.2 may be an epiphenomenon in the progression from adenoma to carcinoma, as suggested previously, 24 , 25 CN gain in the carcinomatous component may play a role in colorectal carcinogenesis. SCNAs may become candidate molecular markers predicting the risk of progression from adenoma to carcinoma.…”

“…Recently, we found that a specific genotype defined by SCNAs with altered expression of the corresponding gene plays an important role in CRC progression 25 . In the present study, we showed that five genotypes involving CN gain with upregulated expression of the corresponding gene ( RPS21, MIR3654, RSP20, SNORD54 , and ASPH ) are closely associated with progression from the adenomatous to carcinomatous component of the same tumor.…”

“…SCNAs may become candidate molecular markers predicting the risk of progression from adenoma to carcinoma. 24 , 25 , 26 …”

Cribriform-type adenocarcinoma of the colorectum: comprehensive molecular analyses of a distinctive histologic subtype of colorectal cancer

“…Identification of target genes will require both genomic and functional studies ( 25 ). For focal events, the copy number profiles of higher resolution analysis can help narrow the list of candidates ( 26 ). However, we could not find correlations between the region displaying SCNAs at 2p14-16 with corresponding gene expression, which may suggest that genomic changes derived from cancer cells occur randomly during neoplastic progression, regardless of functional alterations in mRNA expression.…”

Quantitative Proteomic Analysis of Synovial Tissue Reveals That Upregulated OLFM4 Aggravates Inflammation in Rheumatoid Arthritis

“…Human OLFM4, originally termed human cloned from myeloid precursor cells after granulocyte colony-stimulating factor stimulation, is a secreted glycoprotein more commonly known as the antiapoptotic molecule GW112 . More recently, upregulated OLFM4 expression has been described in lung and breast, prostatic, gastric, , and pancreatic , cancers and in colorectal adenomas, , and it has been suggested that OLFM4 is involved in cellular processes, such as apoptosis and tumor growth …”