[Circadian and ultradian cycles in narcolepsy].

OBJECTIVE

After BRCA 1&2, CHEK2 is the most frequently predisposing altered gene causing  breast cancer in female. The prime objective of the current study was to analyze germline CHEK2 variants and their association with breast cancer in Balochistani population.

METHODS

Breast cancer is among the most prevalent cancers worldwide and most common diagnosed cancer in women. Mutations in many proto-oncogenes and tumor suppressor genes lead to the development of cancer. Along with the highly penetrance genes BRCA1 and BRCA2 increase the risk of breast cancer, mutations in other genes including CHEK2, a tumor suppressor gene have also been reported to be associated with breast cancer. In current study CHEK2 gene was analyzed for variation in breast cancer patients and controls of Balochistani population. Sequencing results of the DNA samples of the registered cases of breast cancer in CENAR were analyzed using Chromas software and bioinformatics tools including BLAT and  RNAfold web server.

RESULTS

An intronic variant c.319+38-43dupA falling 38 nucleotide away at splice donor site of the CHEK2 gene exon 2,  in 9%  breast cancer cases, was identified which has also been previously reported in non-Hodgkin Lymphoma cases. All the cases with identified variant, were affected with invasive ductal carcinoma. Higher tumor grade (III) was reported in >50% of the patients and > 70% of patients diagnosed with advanced stage of cancer. The RNA prediction results revealed the variant falling in the intronic region may code for miRNA that could play an important role in cancer progression.

CONCLUSION

Our results suggest that the intronic variant identified in breast cancer cases as well as reported previously may act as a cancer marker and causing a splice site disruption or altering the posttranscriptional modification of mRNA encoded by CHEK2 gene.