Abstract
BackgroundThe aim of this study was to determine the clinicopathological features of gastric cancers with loss of imprinting (LOI) of LIT1. Insulin-like growth factor 2 (IGF2) and H19 in Chinese patients.MethodsDNA and RNA from tumours were amplified and then digested with RsaI, ApaI and HinfI, and RsaI respectively to determine the LOI status. The demographic and clinicopathological characteristics in LOI positive and LOI negative patients were compared and tested with Statistical analysis.ResultsOf the 89 patients enrolled for analysis, 22, 40 and 35 were heterozygous and thus informative for LIT1, IGF2 and H19 LOI analyses respectively. The positive rate of LIT1, IGF2 and H19 LOI of gastric cancer tissues were 54.6% (12/22), 45% (18/40) and 8.6% (3/32) in Chinese patients. Gastric corpus cancer (8/10, 80%) were more likely to have LOI of IGF2 in tumours than antrum cancers (10/30, 33.3%){odds ratio (OR) = 8, 95% confidence intervals (CI) = 1.425-44.920, p = 0.018)}. LOI of IGF2 in tumours was also associated with the lymph node metastasis (LNM) (OR = 4.5, 95% CI = 1.084-18.689, p = 0.038).ConclusionIGF2 LOI is present in high frequency in Chinese gastric cancer patients, especially those with gastric corpus cancer.
Highlights
The aim of this study was to determine the clinicopathological features of gastric cancers with loss of imprinting (LOI) of LIT1
Insulin-like growth factor 2 (IGF2) LOI is present in high frequency in Chinese gastric cancer patients, especially those with gastric corpus cancer
Loss of imprinting at LIT1, IGF2 and H19 in gastric cancer tissues We examined the status of genomic imprinting of the LIT1, IGF2 and H19 genes in 89 gastric cancers by PCRrestriction fragment length polymorphism (RFLP) analysis (Fig. 1, Fig. 2, Fig. 3)
Summary
The aim of this study was to determine the clinicopathological features of gastric cancers with loss of imprinting (LOI) of LIT1. Genomic imprinting is an epigenetic modification that leads to the preferential or exclusive expression of a gene from one of the two parental alleles in somatic cells [1]. Abnormal imprinting involved in a number of human diseases, LOI is one of the most frequent genetic alterations in cancers [2]. LOI can result in either activation or silencing of the normally silent or expressed allele of a growth promoting gene or a growth inhibitory gene, respectively. The cluster of imprinted genes on human chromosome 11p15.5 comprises two imprinted domains: the IGF2-H19 domain and the KCNQ1 domain [4]. H19 and IGF2 genes are imprinted genes and expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin [5]; normally IGF2 expression is coordinately regu-
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