RET mutations in a large indian family with medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a tumor arising from the para follicular (C) cells of the thyroid gland and can occur either sporadically or as part of an inherited syndrome. A proportion of these cases carry an autosomal dominant mutation in the RET (REarranged during Transfection) proto-oncogene. Screening for these mutations in the affected patients and the carriers "at risk" which includes the first-degree relatives is of utmost importance for early detection and prompt treatment including prophylactic thyroidectomy in cases that harbor these mutations. RESULTS: This report presents details of screening and subsequent follow-up of a large Indian family, where the index case was found to carry p. Cys634Ser mutation involving exon 11 of the RET gene. These data are of value considering the paucity of information within the region in context of screening large families affected by these mutations.

Molecular characteristics of meningiomas in a cohort of Indian patients: loss of heterozygosity analysis of chromosomes 22, 17, 14 and 10.

BACKGROUND: Though, loss of heterozygosity (LOH) at chromosome 22q is considered to be the most likely initiating event in the formation of meningiomas, LOH at other chromosomes (1, 3, 6, 9, 10, 11, 14.17, and 18) have been implicated in its progression. The aim of this study was to analyze microsatellite markers on a select set of chromosomes including, 22q, 10q, 14q, and 17p for LOH in patients with meningiomas. MATERIALS AND METHODS: Tumor tissue and its corresponding blood sample were collected from 27 patients with meningioma. Four polymorphic microsatellite markers (D10S520, D17S1289, D14S555, and D22S417) were characterized for LOH analysis. RESULTS: There were 14 World Health Organization (WHO) grade I, 12 WHO grade II and 1 WHO grade III meningiomas. LOH was seen most often at D22S417 with an equal distribution between the grades (33% of informative samples in each grade). Though, LOH at D14S555 was seen in 50% of informative WHO grade II tumors, compared to 11.1% of informative WHO grade I tumors it did not reach statistical significance. However, allelic imbalance (AI) at D14S555 was significantly associated with atypia (P = 0.05). LOH at D17S1289 was seen only in one tumor sample, and none of the informative samples displayed LOH at D10S520. CONCLUSION: The frequency and equal distribution of LOH at chromosome 22 supports the hypothesis that it is an early event in the tumorigenesis of meningiomas. The association of AI at D14S555 in WHO grade II meningiomas needs to be investigated on a larger set of samples.

Comparison of 11 endogenous control genes for normalization of mRNA obtained from paraffin-embedded tissues.

Real-time reverse transcriptase PCR (RT-PCR) based assays are being increasingly used in characterization of gene expression. Good quality mRNA is an essential prerequisite for such assays. While fresh tissues provide quality mRNA, the same may not be true of tissues which are formalin-fixed and paraffin-embedded (FFPE). This emphasizes the need to identify a good endogenous control gene to normalize for differences in quality and RNA recovery. We attempted to characterize gene expression patterns of 11 commonly used endogenous control genes among 20 FFPE tissues (both neoplastic and normal). Pearson's coefficient of correlation was determined by comparing the expression of each gene against the mean expression of all other genes. beta2 microglobulin (beta2M) and beta-actin (betaA) (r = 0.95 and 0.94, respectively) were found to be stably expressed across all tissues. However, betaA had greater accuracy (2 x SD) than beta2M and therefore may be a better choice of an endogenous control for experiments that require normalization while using FFPE tissues.