Detection Of Genetic Alterations In Gastric Cancer Patients From Saudi Arabia Using Comparative Genomic Hybridization (Cgh)

The publisher required to make research data available open access repository ( Availability statement: All data will be submitted to public repository and will be available after acceptance of manuscript). Abstract Background: The 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. Methods: Formalin-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. Results: Copy 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.出版方要求将研究数据提交至开放获取仓储（可用性声明：所有研究数据将被提交至公共仓储，并在稿件录用后对外公开）。 摘要 背景：本研究旨在探寻与胃癌（gastric cancer, GC）相关的DNA拷贝数变异（copy number variations, CNVs）等基因组失衡现象，并分析沙特人群中这类变异与胃癌发生进程中相关基因的关联。 方法：本研究收集了33例胃癌患者的福尔马林固定石蜡包埋（Formalin-fixed paraffin-embedded, FFPE）组织样本，以及15例正常胃组织样本。对早、晚期胃癌样本进行基因分型，并通过Illumina HumanOmni1-Quad v1.0 微珠芯片（BeadChip）对拷贝数变异进行检测。 结果：相较于正常组织样本，所有胃癌样本中的拷贝数扩增事件发生率均高于缺失事件。每例样本的平均染色体改变数目为：扩增64个，缺失40个；拷贝数异常片段的中位长度为：扩增679115bp，缺失375889bp。本研究共鉴定出7例高拷贝扩增、52例拷贝扩增、14例拷贝缺失、32例纯合缺失，以及10例拷贝中性杂合性缺失（loss of heterozygosities, LOH）。 拷贝数扩增事件常见于以下染色体区域：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；而拷贝数缺失事件则常见于1p36.23、1p36.32、1p32.1、1q44、3q25.2、6p22.1、6p21.33、8p11.22、10q22.1、12p11.22、14q32.12及16q24.2区域。本研究还鉴定出2例14号染色体与22号染色体单体性、52例部分三体性，以及22例4号整条染色体中性杂合性缺失，涉及区域包括13q14.2-q21.33、5p15.2-p15.1、5q11.2-q13.2、5q33.1-q34与3p14.2-q13.12。此外，在11例不同胃癌样本中均检测到1p36.32区域的11次扩增与2次缺失，该区域此前未在其他人群中被报道过。统计学分析证实，与对照组及其他分期的胃癌患者相比，幽门螺杆菌（H. pylori）感染与胃癌T4分期存在显著关联。