Detection of genetic alterations in gastric cancer patients from Saudi Arabia using comparative genomic hybridization (CGH)

Abstract

BackgroundThe present study was conducted to discover genetic imbalances such as DNA copy number variations (CNVs) associated with gastric cancer (GC) and to examine their association with different genes involved in the process of gastric carcinogenesis in Saudi population.MethodsFormalin-fixed paraffin-embedded (FFPE) tissues samples from 33 gastric cancer patients and 15 normal gastric samples were collected. Early and late stages GC samples were genotyped and CNVs were assessed by using Illumina HumanOmni1-Quad v.1.0 BeadChip.ResultsCopy number gains were more frequent than losses throughout all GC samples compared to normal tissue samples. The mean number of the altered chromosome per case was 64 for gains and 40 for losses, and the median aberration length was 679115bp for gains and 375889bp for losses. We identified 7 high copy gain, 52 gains, 14 losses, 32 homozygous losses, and 10 copy neutral LOHs (loss of heterozygosities). Copy number gains were frequently detected at 1p36.32, 1q12, 1q22, 2p11.1, 4q23-q25, 5p12-p11, 6p21.33, 9q12-q21.11, 12q11-q12, 14q32.33, 16p13.3, 17p13.1, 17q25.3, 19q13.32, and losses at 1p36.23, 1p36.32, 1p32.1, 1q44, 3q25.2, 6p22.1, 6p21.33, 8p11.22, 10q22.1, 12p11.22, 14q32.12 and 16q24.2. We also identified 2 monosomy at chromosome 14 and 22, 52 partially trisomy and 22 whole chromosome 4 neutral loss of heterozygosities at 13q14.2-q21.33, 5p15.2-p15.1, 5q11.2-q13.2, 5q33.1-q34 and 3p14.2-q13.12. Furthermore, 11 gains and 2 losses at 1p36.32 were detected for 11 different GC samples and this region has not been reported before in other populations. Statistical analysis confirms significant association of H. pylori infection with T4 stage of GC as compare to control and other stages.ConclusionsWe found that high frequency of copy number gains and losses at 1p36.23, 1p32.1, 1p36.32, 3q25.2, 6p21.33 and 16q24.2 may be common events in gastric cancer. While novel CNVs at 1p36.32 harbouring PRDM16, TP73 and TP73-AS1 genes showed 11 gains and 2 losses for 11 different GC cases and this region is not reported yet in Database of Genomic Variants may be specific to Saudi population.

The Role of Human Satellite III (1q12) Copy Number Variation in the Adaptive Response during Aging, Stress, and Pathology: A Pendulum Model

“…Samples from 33 gastric cancer patients were collected in Saudi Arabia and analyzed using CGH compared to 15 normal gastric samples from the same population. The study revealed frequently copy number gains within several chromosomal regions including 1q12 among the most frequent [83]. Other findings of 1q overrepresentation in various types of cancer were obtained by increasing in situ hybridized site numbers in lymphoma and myeloma [84] and hepatitis B virus-related hepatocellular carcinoma [85].…”

H. pylori infection alters repair of DNA double-strand breaks via SNHG17

“…Some inhibitors designed as cancer therapeutics specifically targeting DSB repair proteins have been reported (52,53). However, DSB repair pathway selection and the associated factors remain poorly defined, especially regarding the mechanism by which H. pylori infection (62). The API2-MALT1 fusion gene was originally identified from a t(11;18)(q21;q21) translocation, a specific chromosomal abnormality that is found in mucosa-associated lymphoid tissue (MALT) lymphoma.…”

Multifaceted Role of PRDM Proteins in Human Cancer

“…Knockdown of these two genes synergistically restored TGF-β responsiveness in gastric cancer cells and reduced tumor growth in vivo; biochemical analysis demonstrated that MEL1/PRDM16 interacted with SKI and inhibited TGF-β signaling by stabilizing the inactive Smad3-SKI complex on the promoter of TGF-β target genes ( Figure 3D) [251]. Similarly, PRDM16 high copy gain was also observed in a small cohort using CGH [252]. Otherwise, a more recent study showed that miR-214 was able to inhibit PRDM16 expression thus promoting the proliferation and migration of gastric cancer cells and enhancing the Warburg effect ( Figure 3H) [253].…”