Chromosome 8q as the most frequent target for amplification in early gastric carcinoma

Abstract

Early gastric carcinoma (GC) is considered to be a curable cancer, as it progresses to the advanced stage following varying durations. Understanding the early stage of GC may provide an insight into its pathogenesis and contribute to reducing the mortality rate of this disease. To investigate the genomic aberrations associated with 22 cases of early GC, high-density microarray comparative genomic hybridization was performed in the present study. The most notable finding was copy number gains (log2 ratio >0.25) on the long arm of chromosome 8, which occurred in 77.3% (17/22) of GC cases, and the delineated minimal common region was 8q22.1-q24.3. More specifically, two amplified (log2 ratio >1) loci in the 8q22.1-q24.3 region were detected in 18.2% (4/22) of GC cases. The first loci covered a region of 102.4–107.9 kb, mapping on 8q22.3-q23.1, and comprised the transcription factor CP2-like 3 gene. The second loci, spanning 128.7–145.7 kb on 8q24.21-q24.3, comprised the representative oncogene of myelocytomatosis. Furthermore, the following possible target genes that were not previously considered to play a pathogenic role in GC were identified: Plasmacytoma variant translocation 1, cysteine/histidine rich 1, kinesin family member C2, forkhead box H1, protein phosphatase 1 regulatory subunit 16A, glutamic-pyruvate transaminase, LOC113655 and RecQ protein-like 4. In the present study, previous findings showing that 8q mutations accumulate early during the multistage pathogenesis of GC were confirmed and expanded upon. The confirmation of previously reported 8q gains and the identification of novel target genes at 8q22.1-q24.3 amplified chromosomal sites should aid in improving our understanding of the molecular mechanisms underlying the tumorigenesis of early GC.

Diverse expression patterns of the EMT suppressor grainyhead‐like 2 (GRHL2) in normal and tumour tissues

“…The 8q22 chromosomal region harbouring the GRHL2 gene frequently is amplified in a variety of human malignancies including prostate cancer, gastric cancer, HCC, and breast cancer . Amplified and overexpressed genes from chromosome 8q22 were associated with de novo chemoresistance and metastatic recurrence of breast cancer, suggesting that genes located in this chromosomal region significantly influence malignant phenotype and poor clinical outcome.…”

Association of common variants on chromosome 8q24 with gastric cancer in Venezuelan patients

“…Furthermore, recent studies revealed that copy number gains of genes located at 8q24 is an early event during the multistage pathogenesis of gastric cancer (Kang, 2014), and is associated with poor survival patients with gastric cancer (Wang et al, 2015). In addition, the association of common polymorphisms located at chromosome 8q24 with the risk of prostate, breast, colorectal and thyroid follicular tumors has suggested a role for these variants in the formation of multiple adenomas (Berndt et al, 2008).…”

Case Report: Analysis of Circulating Tumor Cells in a Triple Negative Spindle-Cell Metaplastic Breast Cancer Patient

“…Amplification of chromosome 8q regions has been described in numerous cancer types, such as hepatocellular carcinoma ( 23 ), gastric cancer ( 24 ), clear cell renal carcinoma ( 25 ), and BC ( 26 ). In particular, in BC, 8q is considered a hotspot site of amplification associated with unfavorable prognosis ( 27 ) and, accordingly in our study, poor response to NAC ( 28 ), in part due to the location of c-myc locus in 8q24.1, near 8q24.22–8q24.23.…”