Down regulation of KLK7 expression in breast tissues and identification of a novel spliced KLK7 mRNA

Background: Alternative splicing commonly occurs in cancer cells and many cancer specific splice variants have been reported as potential candidate biomarkers of the disease. We have studied human tissue Kallikrein 7 (KLK7) mRNA expression profile in breast cancer patients of our region. KLK7 is member of a multi-gene family consisting of 15 members (KLK1-KLK15). Methods: We optimized touch down nested PCR method for the amplification of KLK7 isoforms/variants. Various bioinformatics tools were used for sequence analysis, identification of splicing pattern and prediction of encoded proteins. Results: We observed an unusual splicing event consisting of exon 3 (E3) truncation at 3' end (by 124 nucleotides), exon 4 (E4) exclusion and exon 5 (E5) truncation at 5' end (by 33 nucleotide) in 2 normal breast tissues, one obtained from invasive ductal carcinoma grade II patient and other collected from mammary dysplasia patient. Moreover, 3 other KLK7 mRNAs (KF963190, KF963191, and KF963193) expressed in breast cancer were noticed to exhibit single nucleotide polymorphism (SNPs). Bioinformatic analysis revealed that the alternatively spliced mRNA (KF963192) will potentially encode a truncated and non-functional protein. Similarly although encoded proteins have considerable homology with normal hK7 protein, SNPs seem to cause great variations in pIs, structures and molecular weights of encoded proteins. Conclusions: There is need to further explore the impact of the unique splicing event, SNPs and characterize these population specific mutations and their possible role in the pathogenesis of breast cancer (AU)

Extra nodal lymphoma

To study the different clinical presentations and treatment options of extra nodal lymphoma. Prospective. Surgical Unit, Bhawal Victoria Hospital, Bahawalpur from May 01,2000 to April 30,2004. Patients of either sex and age diagnosed as case of extra nodal lymphoma were included in the study. The clinical record of the patients included biodata, symptoms and signs, biopsy report, biochemical and radiology report, treatment [surgery, chemotherapy, radiotherapy] given and follow up. In this study we had 13 patients. Out of these 4[31%] were female and 9[69%] were male. Extra nodal sites included GIT [54%], testis [15%] spinal cord [15%] and skin [15%]. The prognosis in most of the cases was not so good. Due to this extensive presence of lymphatic tissue, lymphoma can develop in and spread to, almost any part of the body, For the treatment purpose staging of the disease is very important like any cancer, the earlier the lymphoma is diagnosed, the easier it is to treat