The Association between DNA Copy Number Aberrations at Chromosome 5q22 and Gastric Cancer

Abstract

BackgroundGastric cancer is common cancer. Discovering novel genetic biomarkers might help to identify high-risk individuals. Copy number variation (CNV) has recently been shown to influence risk for several cancers. The aim of the present study was sought to test the association between copy number at a variant region and GC.MethodsA total of 110 gastric cancer patients and 325 healthy volunteers were enrolled in this study. We searched for a CNV and found a CNV (Variation 7468) containing part of the APC gene, the SRP19 gene and the REEP5 gene. We chose four probes targeting at APC-intron8, APC-exon9, SRP19 and REEP5 to interrogate this CNV. Specific Taqman probes labeled by different reporter fluorophores were used in a real-time PCR platform to obtain copy number. Both the original non-integer data and transformed integer data on copy number were used for analyses.ResultsGastric caner patients had a lower non-integer copy number than controls for the APC-exon9 probe (Adjusted p = 0.026) and SRP19 probe (Adjusted p = 0.002). The analysis of integer copy number yielded a similar pattern although less significant (Adjusted p = 0.07 for APC-exon9 probe and Adjusted p = 0.02 for SRP19 probe).ConclusionsLosses of a CNV at 5q22, especially in the DNA region surrounding APC-exon 9, may be associated with a higher risk of gastric cancer.

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

“…52 Its protein product negatively regulates WNT signaling and its inactivation leads to β-catenin accumulation and transcriptional activation of genes (MYC, cyclin D1) related to cell proliferation. 53,54 As reported, the chromosome locus of APC is frequently deleted in GCs, [55][56][57][58][59] and its decreased copy number significantly associated with lymph node invasion and metastasis in GC patients. 55 Moreover, APC deletion was principally found in advanced GCs, suggesting that it might be involved in the progression but not initiation of GCs.…”

“…53,54 As reported, the chromosome locus of APC is frequently deleted in GCs, [55][56][57][58][59] and its decreased copy number significantly associated with lymph node invasion and metastasis in GC patients. 55 Moreover, APC deletion was principally found in advanced GCs, suggesting that it might be involved in the progression but not initiation of GCs. Furthermore, in a study concerning 131 sporadic gastric adenocarcinoma samples with matched normal tissues, Fang et al 60 demonstrated APC copy number deletions were found in a relatively high percentage (25.9%) and were associated with lymph node invasion or metastasis of GC.…”

CNVs Associated with Susceptibility to Cancers: A Mini-Review

“…However, we have found one report on CNVs associated with gastric cancer. Tsai et al reported that a loss of a CNV at 5q22 including APC-exon 9 gives rise to a high risk of the disease [50].…”

Acquisition of genomic events leading to lymphoblastic transformation in a rare case of myeloproliferative neoplasm with BCR–JAK2 fusion transcript

“…). Other acquired abnormalities were a gain of the long arm of chromosome 6 and deletion of the APC gene previously reported in solid tumors (Table S1). The patient was treated with polychemotherapy (prednisone, vincristine, daunorubicin, cyclophosphamide, and l ‐asparaginase) and addition of the anti‐JAK2 drug ruxolitinib (2 × 10 mg/day) allowing the achievement of complete remission.…”