Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2009 Jun 30

PMID 19561646

Citations 31

Authors

N Narita

A Tanemura

R Murali

R A Scolyer

S Huang

T Arigami

S Yanagita

K K Chong

J F Thompson

D L Morton

D S Hoon

Affiliations

Soon will be listed here.

Abstract

RET proto-oncogene encodes a receptor tyrosine kinase whose ligand is glial cell line-derived neurotrophic factor (GDNF), and its polymorphism at G691S juxtamembrane region (RETp) is a germline polymorphism. Cutaneous melanomas, particularly the desmoplastic subtype, are highly neurotropic; thus we sought to determine the frequency of RETp in cutaneous melanoma and its functional responsiveness to GDNF. RETp was assessed in 71 non-desmoplastic cutaneous melanomas (non-DMs) and 70 desmoplastic melanomas (DMs). Melanoma cell lines with RETp, RET wild type (RETwt), BRAF V600E mutation (BRAFmt) or BRAF wild type (BRAFwt) were assessed for functional activity. RETp frequency was significantly higher in DMs (61%) than in non-DMs (31%, P<0.001). BRAFmt was detected in only 11% of DMs. GDNF stimulation significantly amplified cell proliferation, migration and invasion in RETp, but not in RETwt melanoma cells. GDNF stimulation of RETp cell lines enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt of the RET-RAS-RAF-ERK and RET-phosphatidylinositol 3-kinase (PI3K)-Akt pathways, respectively. GDNF response of RETp cells in signal transduction and other functional studies were not affected by BRAFmt. The study demonstrates that RETp is frequently found in cutaneous melanoma, particularly desmoplastic subtypes, and responds to GDNF inducing events favorable for tumor progression.

Citing Articles

Genomic and transcriptomic analyses unveil the genetic basis of green shank trait in small white-feather chickens.

Kong S, Cai X, Cai B, Xian Y, Zhou Z, Cai D Poult Sci. 2025; 104(4):104912.

PMID: 39985900 PMC: 11904536. DOI: 10.1016/j.psj.2025.104912.

Pralsetinib: chemical and therapeutic development with FDA authorization for the management of RET fusion-positive non-small-cell lung cancers.

Ali F, Neha K, Chauhan G Arch Pharm Res. 2022; 45(5):309-327.

PMID: 35598228 DOI: 10.1007/s12272-022-01385-3.

Targeting Rearranged during Transfection in Cancer: A Perspective on Small-Molecule Inhibitors and Their Clinical Development.

Saha D, Ryan K, Lakkaniga N, Acharya B, Garcia Garcia N, Smith E J Med Chem. 2021; 64(16):11747-11773.

PMID: 34402300 PMC: 9697126. DOI: 10.1021/acs.jmedchem.0c02167.

LncRNA-HNF1A-AS1 functions as a competing endogenous RNA to activate PI3K/AKT signalling pathway by sponging miR-30b-3p in gastric cancer.

Liu H, Ma R, Lv B, Zhang H, Shi D, Guo X Br J Cancer. 2020; 122(12):1825-1836.

PMID: 32336754 PMC: 7283217. DOI: 10.1038/s41416-020-0836-4.

Oncogenic and drug-sensitive RET mutations in human epithelial ovarian cancer.

Guan L, Li Z, Xie F, Pang Y, Zhang C, Tang H J Exp Clin Cancer Res. 2020; 39(1):53.

PMID: 32293499 PMC: 7092606. DOI: 10.1186/s13046-020-01557-3.

References

Weber F, Eng C . Update on the molecular diagnosis of endocrine tumors: toward -omics-based personalized healthcare?. J Clin Endocrinol Metab. 2008; 93(4):1097-104. DOI: 10.1210/jc.2008-0212. View

Gumireddy K, Sun F, Klein-Szanto A, Gibbins J, Gimotty P, Saunders A . In vivo selection for metastasis promoting genes in the mouse. Proc Natl Acad Sci U S A. 2007; 104(16):6696-701. PMC: 1871848. DOI: 10.1073/pnas.0701145104. View

Livestro D, Muzikansky A, Kaine E, Flotte T, Sober A, Mihm Jr M . Biology of desmoplastic melanoma: a case-control comparison with other melanomas. J Clin Oncol. 2005; 23(27):6739-46. DOI: 10.1200/JCO.2005.04.515. View

Elisei R, Cosci B, Romei C, Bottici V, Sculli M, Lari R . RET exon 11 (G691S) polymorphism is significantly more frequent in sporadic medullary thyroid carcinoma than in the general population. J Clin Endocrinol Metab. 2004; 89(7):3579-84. DOI: 10.1210/jc.2003-031898. View

Goto Y, Arigami T, Kitago M, Nguyen S, Narita N, Ferrone S . Activation of Toll-like receptors 2, 3, and 4 on human melanoma cells induces inflammatory factors. Mol Cancer Ther. 2008; 7(11):3642-53. PMC: 3480738. DOI: 10.1158/1535-7163.MCT-08-0582. View

Sawai H, Okada Y, Kazanjian K, Kim J, Hasan S, Hines O . The G691S RET polymorphism increases glial cell line-derived neurotrophic factor-induced pancreatic cancer cell invasion by amplifying mitogen-activated protein kinase signaling. Cancer Res. 2005; 65(24):11536-44. DOI: 10.1158/0008-5472.CAN-05-2843. View

Davison J, Rosenbaum E, Barrett T, Goldenberg D, Hoque M, Sidransky D . Absence of V599E BRAF mutations in desmoplastic melanomas. Cancer. 2005; 103(4):788-92. DOI: 10.1002/cncr.20861. View

Jaroszewski D, Pockaj B, DiCaudo D, Bite U . The clinical behavior of desmoplastic melanoma. Am J Surg. 2002; 182(6):590-5. DOI: 10.1016/s0002-9610(01)00819-4. View

Takahashi M, Buma Y, Iwamoto T, Inaguma Y, Ikeda H, Hiai H . Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene. 1988; 3(5):571-8. View

10.

Shinozaki M, Fujimoto A, Morton D, Hoon D . Incidence of BRAF oncogene mutation and clinical relevance for primary cutaneous melanomas. Clin Cancer Res. 2004; 10(5):1753-7. DOI: 10.1158/1078-0432.ccr-1169-3. View

11.

Kondo T, Ezzat S, Asa S . Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 2006; 6(4):292-306. DOI: 10.1038/nrc1836. View

12.

Busam K, Zhao H, Coit D, Kucukgol D, Jungbluth A, Nobrega J . Distinction of desmoplastic melanoma from non-desmoplastic melanoma by gene expression profiling. J Invest Dermatol. 2005; 124(2):412-8. DOI: 10.1111/j.0022-202X.2004.23600.x. View

13.

Curtin J, Busam K, Pinkel D, Bastian B . Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006; 24(26):4340-6. DOI: 10.1200/JCO.2006.06.2984. View

14.

Satyamoorthy K, Li G, Gerrero M, Brose M, Volpe P, Weber B . Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res. 2003; 63(4):756-9. View

15.

Fujiwara Y, Chi D, Wang H, Keleman P, Morton D, Turner R . Plasma DNA microsatellites as tumor-specific markers and indicators of tumor progression in melanoma patients. Cancer Res. 1999; 59(7):1567-71. View

16.

Selek U, Chang E, Hassenbusch 3rd S, Shiu A, Lang F, Allen P . Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases. Int J Radiat Oncol Biol Phys. 2004; 59(4):1097-106. DOI: 10.1016/j.ijrobp.2003.12.037. View

17.

Quinn M, Crotty K, Thompson J, Coates A, OBrien C, McCarthy W . Desmoplastic and desmoplastic neurotropic melanoma: experience with 280 patients. Cancer. 1998; 83(6):1128-35. View

18.

Takahashi M . The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev. 2001; 12(4):361-73. DOI: 10.1016/s1359-6101(01)00012-0. View

19.

Runeberg-Roos P, Saarma M . Neurotrophic factor receptor RET: structure, cell biology, and inherited diseases. Ann Med. 2007; 39(8):572-80. DOI: 10.1080/07853890701646256. View

20.

Umetani N, Mori T, Koyanagi K, Shinozaki M, Kim J, Giuliano A . Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer. Oncogene. 2005; 24(29):4721-7. DOI: 10.1038/sj.onc.1208538. View