Endocrinol Metab.  2012 Sep;27(3):173-179. 10.3803/EnM.2012.27.3.173.

RET: A Multi-Faceted Gene in Human Cancer

• Santoro M
• Carlomagno F
• Melillo RM

• KMID: 2282399
• DOI: http://doi.org/10.3803/EnM.2012.27.3.173

Abstract

REarranged during Transfection (RET) gene encodes a receptor tyrosine kinase and it was initially discovered as an in vitro transforming gene. For many years, RET has been involved in papillary thyroid carcinoma and medullary thyroid carcinoma. More recently, lung adenocarcinoma and chronic myelomonocytic leukemia samples have been found to display RET gene rearrangements. This knowledge is stimulating the search for protein kinase inhibitors to combat RET-driven malignancies.

Keyword

Kinase; Neoplasms; Oncogenes; Rearranged during transfection; Signal transduction; Thyroid

MeSH Terms

Adenocarcinoma
Carcinoma
Gene Rearrangement
Humans
Leukemia, Myelomonocytic, Chronic
Lung
Lung Neoplasms
Oncogenes
Phosphotransferases
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
Signal Transduction
Thyroid Gland
Thyroid Neoplasms
Transfection
Adenocarcinoma
Carcinoma
Lung Neoplasms
Phosphotransferases
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
Thyroid Neoplasms

Figure

• 

  Fig. 1 Schematic drawing of the RET gene (upper) and protein (lower). RET gene structure with coding exons is represented; nucleotide (nt) positions are marked. An alternative splicing in exon 19 generate two alternative mRNAs, coding for RET-51 (1,114 residues), when exon 19 is spliced to exon 20, or RET-9 (1,072 residues), when exon 19 remains unspliced. Last coding exon (exon 21) that encodes the C-terminal part of another less abundant RET isoform, RET (43), is not represented. Position of the STOP codons for RET-51 and RET-9 is marked. RET protein is represented in the bottom part of the figure. The extracellular RET domain (with the signal peptide [SP], four cadherin-like repeats [CLD1-4] and a cysteine-rich domain [CRD]), the transmembrane domain (TM), and the intracellular tyrosine kinase domain (TK) are represented. The RET-TK is split into two subdomains (TK1 and 2) by an insert region (KI). The position of most common RET point mutations associated to familial and sporadic MTC is shown. The breakpoint in RET (at the boundary between exons 11 and 12), that is involved in RET gene rearrangements in papillary thyroid carcinoma, lung adenocarcinoma, and chronic myelomonocytic leukemia, is represented. All these informations were retrieved from National Center for Biotechnology Information, with the exception of RET kinase insert boundaries that were retrieved from Knowles et al. [17] and cadherin-like domain boundaries that were retrieved from Scott et al. [16].

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