RET mutation status in medullary thyroid cancer(MTC) patients and the significance of genetic screening for mutations in their immediate relatives--a preliminary report.

Multiple Endocrine Neoplasia (MEN) 2A is an inherited disease characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma(PHCH) and hyperparathyroidism(HPT). It has recently been shown to be associated with germline mutations in the RET proto-oncogene. Genetic testing for RET mutations will, therefore allow the identification of people with asymptomatic MEN 2 who can be offered prophylactic thyroidectomy and biochemical screening as preventive measures. No genetic study based on RET mutation detection has been available in India so far. The aim of the present study is to detect the proportion of MTC cases having inherited germline or somatic RET mutations and to identify family members at risk for MEN and, thereby the feasibility of screening for MEN. DNA extracted from the peripheral blood and somatic (tumor) tissues were subjected to PCR using primers for exons 10,11 and 16. A few samples were subjected to direct sequencing. Germline mutations were identified in 3 of 4 MEN 2A patients, 18 of 24 sporadic MTC(SMTC), 2 of 4 children of MEN2A and 8 relatives of SMTC. Common mutation was in exon 10 and 11 (c634). It is recommended that RET mutation analysis and counseling of patients and their immediate relatives be introduced on a regular basis to identify gene carriers.

Telomerase and telomere length in normal and malignant human endometrium as prognostic markers.

Telomerase activation and telomere length maintainence are thought to be essential for cellular immortality and oncogenesis. Normal human endometrium expresses significant telomerase activity in a menstrual phase dependent manner. In this report, we have evaluated telomerase activity and telomere length in post menopausal endometrial hyperplasias and endometrial cancers to study their usefulness as prognostic markers. Telomerase activity was measured by the TRAP assay (Boehringer Mannheim, Germany) and telomere restriction fragment (trf) by the telomere length assay kit (BD Pharmingen). Proliferation markers PCNA and Bcl2 were studied by immunohistochemistry. Senescence associated Ogal activity was studied simultaneously and correlated with the above markers. Strong telomerase activity was observed in the proliferative phase of the normal endometrium, endometrial cancers and post-menopausal endometrial hyperplasias compared to normal, secretory and resting phases of the endometrium. PCNA and Bcl2 showed high positivity in telomerase positive cases. Telomerase activity was inversely proportional to Ogal activity. Mean trf lengths became shortened as the normal tissues underwent neoplastic changes. Our study suggests that high telomerase activity and short telomere lengths could be useful prognostic markers in human endometrium.