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Kandula M.,Krisani Biosciences Private Ltd | Chennaboina K.K.,Krisani Biosciences Private Ltd | Ammi Raju Y.S.,Krisani Biosciences Private Ltd | Raju S.,Nizams Institute of Medical Sciences
Asian Pacific Journal of Cancer Prevention | Year: 2013

Background: The phosphatidylinositol 3-kinase (PI3K) pathway plays a significant role in apoptosis, cellular proliferation and motility. The aim of the present study was to analyze mutations and gene expression profiles of the PI3KCA gene to determine any role in breast carcinomas. Materials and Methods: We analyzed 38 breast cancers for mutations in the two PIK3CA hotspots in exons 9 and 20 by direct sequencing of DNA obtained from biopsy samples. We have also analyzed expression of the PI3KCA gene in 38 breast carcinoma tumor and corresponding control tissue samples at the mRNA level by RT-PCR. The Fisher's exact test (252 only) was performed using MedCalc software for to examine associations with mRNA levels. Results: In the present study a total of 13 cases demonstrated somatic mutations. In 9/13 cases 1633 G>A (E545K) were found in exon 9, whereas in exon 20, 4/13 cases had 3140A>G mutation. Our combined analysis showed PI3KCA mutations present in 34% of human breast cancer patients. In our study, we have also clearly found significantly higher expression in breast cancer tissues in comparison with control tissues (p=0.001). Conclusions: PIK3CA mutation is an emerging tumor marker that, in the future, might be used in the process of choosing a treatment. The detection of PI3KCA mutation might have important clinical implications for diagnosis, progression and therapy.

Kandula M.,Krisani Biosciences Private Ltd | Kalyana Kumar C.,Krisani Biosciences Private Ltd | Ravi Kanth K.,Krisani Biosciences Private Ltd | Laxmi Addala V.,Krisani Biosciences Private Ltd | And 2 more authors.
Journal of Cancer Science and Therapy | Year: 2012

The purpose of this study is to check the similarities of differential gene expression of 11 genes in breast cancer tissue and blood samples from the same individual for early detection of breast cancer. We had investigated differential gene expression by qRT-PCR in 20 breast cancer patients' tumoral tissues and corresponding blood sample. In our analysis BRCA2, HER-2, ER, PR, MET and BRAF mRNA levels were significantly over expressed in tumoral tissues. ER and PR mRNA levels were not detected in any of the peripheral blood samples, whereas KRAS and PTEN mRNA levels were not detected in any of the tumoral tissues. HER-2 (45%), EGFR (40%) and PI3KCA (30%). KRAS and PTEN mRNA levels were significantly over expressed in peripheral blood. In the correlation analysis expression of most of the genes were significantly altered in grade II and III in the tissues, where as in premenopausal women mRNA expression was significantly high in Grade II and III and ER/PR negative tumors. Our results suggests that BRCA2, ER, PR, PI3KCA, MET and BRAF differential gene expression at mRNA levels showed no diagnostic value as a marker of circulating tumour cells in breast cancer. qRT-PCR may be suitable alternative method for the determination of HER-2, EGFR, PI3KCA KRAS and PTEN mRNA status in the blood of breast cancer patients. Premenopausal women with high grade (Grade II and III) and ER/PR negative cases may be associated with proliferation/metastasis, high recurrence rate, and poor prognosis. © 2012 Mahesh K, et al.

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