Dai Zhang1, Zhenning Wang, Yang Luo, Yan Xu, Yanshan Liu, Wei Yang, Xue Zhang. 1. McKusick-Zhang Center for Genetic Medicine and State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Abstract
BACKGROUND AND OBJECTIVES: The molecular genetic alterations leading to gastric malignancy are largely unknown. This study aimed to unravel the genomic DNA copy number aberrations (CNAs) profile during gastric tumorigenesis. METHODS: In this study, we performed genomic profiling in a set of 50 intestinal type gastric carcinomas by a PCR-based relative quantification method, multiple ligation-dependent probe amplification (MLPA) with 112 cancer-related gene loci selected throughout each human chromosome as probes of MLPA assay. RESULTS: Numerous chromosomal DNA CNAs, including gains of 3p22, 4q25, 8q24, 11p13, and 20q13, and losses of 1p36 and 9p21, were identified by MLPA assay as recurrent DNA CNAs in gastric cancer. Moreover, we found the median numbers of gains, losses, and total CNAs were significantly higher in lymph node metastasis positive patients than in cases without metastasis. And gain of 11p13 and losses of 9p21.3, 11q13.3, 17q25.3, and 22q11.23 were associated with lymph node metastasis (P < 0.05). Finally, two major groups, including G1 + 2 with a large number of CNAs and G3 + 4 with a small number of CNAs, can be successfully distinguished by hierarchical cluster analysis. CONCLUSIONS: Our results proved MLPA is a reliable and efficient method to evaluate DNA copy number changes in gastric cancers.
BACKGROUND AND OBJECTIVES: The molecular genetic alterations leading to gastric malignancy are largely unknown. This study aimed to unravel the genomic DNA copy number aberrations (CNAs) profile during gastric tumorigenesis. METHODS: In this study, we performed genomic profiling in a set of 50 intestinal type gastric carcinomas by a PCR-based relative quantification method, multiple ligation-dependent probe amplification (MLPA) with 112 cancer-related gene loci selected throughout each human chromosome as probes of MLPA assay. RESULTS: Numerous chromosomal DNA CNAs, including gains of 3p22, 4q25, 8q24, 11p13, and 20q13, and losses of 1p36 and 9p21, were identified by MLPA assay as recurrent DNA CNAs in gastric cancer. Moreover, we found the median numbers of gains, losses, and total CNAs were significantly higher in lymph node metastasis positive patients than in cases without metastasis. And gain of 11p13 and losses of 9p21.3, 11q13.3, 17q25.3, and 22q11.23 were associated with lymph node metastasis (P < 0.05). Finally, two major groups, including G1 + 2 with a large number of CNAs and G3 + 4 with a small number of CNAs, can be successfully distinguished by hierarchical cluster analysis. CONCLUSIONS: Our results proved MLPA is a reliable and efficient method to evaluate DNA copy number changes in gastric cancers.