The Study Of The Carcinogenesis Of Imprinted Genes Of H19, LIT1 And MEST In Lung Cancer

Genomic imprinting is the new discovery of genetic laws in recent years and is closely linked with the growth and development of embryos, rare genetic diseases and tumors. Many phenomenons beyond the reach of Mendel's Law were explained by genomic imprinting. Its significance is gradually being recognized and the study of it is also increasing deeply. Mendel noted that the traditional rule: the two copies of that alleles those is genetic from the father and mother have the same opportunity to express their pro-generation sources and has nothing to do with the parental source. But in recent years, many studies have found a small portion of the gene expression of these genes is dependent on originated from the mother or the father. That which depends on the expression of pro-allele of this phenomenon is the source of genetic imprinting, which was certain genes - source-dependent expression of a single allele, and the other allele did not express or express extremely weak. This phenomenon is known as genetic imprinting genes. The role of genomic imprinting in the human genetic diseases, particularly in the tumor is causing more and more attention. Accumulating evidence suggests that deregulation of imprinted gene, including loss of imprinting (LOI) that is the biallelic expression of the imprinted gene, plays a role in oncogenesis.H19 gene has been identified on human chromosome 11 for the maternal expression and paternal imprinting source and it is only expressed for the RNA and not translated into protein. the specific functions of H19 have not yet been studied clearly. From many researches, loss of H19 gene has been found not only in childhood tumors but also in common adult cancers. Lit1 is an identified imprinted gene on human chromosome and is expressed preferentially from the paternal allele. Lit1 is the antisense transcription product of the paternal allele of the KvLQT1 gene and related to the maintenance of p57KIP2 genetic imprinting. Mest (Mesoderm-specific transcript) is an imprinted gene expressed from a paternal allele and located on chromosome 7q32. It has been reported that frequent loss of imprinting of the mest gene is often associated with its overexpression in certain malignant tumors. Imprinted genes are the imprinting status change and the relationship between lung cancer and rare reports of foreign and domestic not been reported. It has been rarely reported abroad and never at home about the relationship between lung cancer and the imprinting status of the H19, LIT1 and MEST gene.Objective: To study the loss of imprinting (LOI) H19, LIT1 and MEST genes in lung cancer and the role in carcinogenesis of lung cancer .Methods: Heterozygotes of H19, LIT1 and MEST were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) from 32 tumor samples and corresponding normal tissues. The LOI of H19,LIT1 and MEST genes was detected by reverse transcription- polymerase chain reaction (RT-PCR) and RFLP.Results: Fourteen of 32 cases (48.3%) represented heterozygous informative cases for H19 and LOI of H19 was observed in 4 of the 14(28.6%) informative patients, but not in non-cancerous tissues(P<0.05). Four of 32 cases(12.5%) represented heterozygous informative cases for LIT1 and only one of 4(25%) informative cancers showed biallelic expression of LIT1, while none of 4 matched normal lung tissues showed biallelic expression (P>0.05).The heterozygous informative cases of MEST in 32 cases were 13(40.6%), respectively, seven of 13 informative lung cancer samples showed biallelic expression of MEST(53.8%), whereas no biallelic expression was demonstrated in the corresponding normal tissues (P<0.05).Conclusions: These findings indicated LOI of H19 and MEST took place in lung caners and suggested that LOI of H19 and MEST was involved in the development of lung cancer.