Ret oncogen

Lahr et al.59 Microdissected thyroid tissues PUREscript kit (BlOzym, Germany) Nested PCR, RET oncogene with amplicon size of 141-383 bp Expressed genes can be analyzed from routine FFPE tissue slides or pooled single cells. 

Lahr G, Sticha M, Schtitzea K, et al. Diagnosis of papillary thyroid carcinoma is facilitated by using an RT-PCR approach on laser-microdissected archival material to detect RET oncogene activation. Pathobiology 2000 68 218-226. 

The ret oncogene protein has been demonstrated by immunohistochemistry both in papillary carcinomas and in a subset of hyalinizing trabecular tumors." " However, additional studies are required to ascertain the sensitivity and specificity of currently available ret antibodies in immunohistochemical formats for the identification of papillary carcinomas. 

Nikiforov YE, Rowland JM, Bove KE, et al. Distinct pattern of ret oncogene rearrangements in morphological variants of radiation induced and sporadic thyroid papillary carcinomas in children. Cancer Res. 1997 57 1690-1694. 

Several inherited cancer syndromes are also known to result from mutations in proto-oncogenes. An example is given by the RET proto-oncogene. Depending on the type of mutation and on which part of the gene is affected, RET mutations can lead to multiple endocrine neoplasia 2A or 2B or familial medullary thyroid carcinoma. These familial cancers are inherited in autosomal dominant fashion. A second example is the CDK4 proto-oncogene, which when mutated can cause familial melanoma. 

C) She may have medullary carcinoma of the thyroid. Therefore, serum calcitonin, ret-Pro-Oncogene determination, and ultrasound of the thyroid should be obtained. 

C. Eng. The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung s disease. Seminars in medicine of the Beth Israel Hospital, Boston. NEn J Med, 335 (13), 943-951, 1996. 

Also T. Attie, A. Pelet, P. Edery, C. Eng, L. M. Mulligan, J. Amiel, et al. Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease. Hum Mol Genet, 4 (8), 1381-1386, 1995. 

RET is a human protoonco ne which encodes the RET receptor. There are two forms of receptors with tyrosinekinase activity. They are orphan receptors with unknown ligands. Oncogenic variants are found which are constitutively phosphorylated on tyrosines and form homo-and heterodimers. These variants have been found in endocrine disorders, MEN, and in Hirschsprung s disease. 

Alberti L, Carniti C, Miranda C, et al. RET and NTRKl proto-oncogenes in human diseases. J Cell Physiol 2003 195 168-86. 

Multiple endocrine neoplasia type 2 RET proto-oncogene... 

Other oncogenic mechanisms of RTK activation include mutations in the kinase domain inducing conformational shift of the activation loop and a subsequent constitutive activation as well as constitutive dimerization as the result of a mutation in the extracellular domain of the RTK. Both modes of activation have been observed in germline mutations of the receptor tyrosine kinase Ret, leading to heritable tumor syndromes. 

Functional consequences of each mutation type vary. Generally, mutations result in either activation of the gene, typically forming an oncogene (e.g., KRAS, RET), or loss of function of a tumor suppressor gene TP53, PTEN, CDKNIA). 

Dang GT, Gote GJ, Schultz PN, et al. A codon 891 exon 15 RET proto-oncogene mutation in familial medullary thyroid carcinoma a detection strategy. Mol Cell Probes. 1999 13 77-79. 

Kambouris M, Jackson CE, Eeldman GL. Diagnosis of multiple endocrine neoplasia [MEN] 2A, 2B and familial medullary thyroid cancer [FMTG] by multiplex PCR and heteroduplex analyses of RET proto-oncogene mutations. Hum Mutat. 1996 8 64-70. 

Tallin G, Santoro M, Helie M, et al. RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res. 1998 4 287-294. 

Grieco M, Santoro M, Berlingieri MT, et al. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell. 1990 60 557-563. 

Soares P, Trovisco V, Rocha AS, et al. BRAF mutations and RET/PTC rearrangements all alternative events in the etiopatho-genesis of PTC. Oncogene. 2003 22 4578-4580. 

Eng C. RET proto-oncogene in the development of human cancer. / Clin Oncol. 1999 17 380-393. 

Giordano TJ, Kuick R, Thomas DG, et al. Molecular classification of papillary thyroid carcinoma distinct BRAF, RAS, RET/ PTC mutations-specific gene expression profiles discovered by DNA microarray analysis. Oncogene. 2005 24 6646-6656. 

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