In:
International Journal of Endocrinology, Hindawi Limited, Vol. 2015 ( 2015), p. 1-8
Abstract:
At least 12 genes ( FH, HIF2A, MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and VHL ) have been implicated in inherited predisposition to phaeochromocytoma (PCC), paraganglioma (PGL), or head and neck paraganglioma (HNPGL) and a germline mutation may be detected in more than 30% of cases. Knowledge of somatic mutations contributing to PCC/PGL/HNPGL pathogenesis has received less attention though mutations in HRAS, HIF2A, NF1, RET, and VHL have been reported. To further elucidate the role of somatic mutation in PCC/PGL/HNPGL tumourigenesis, we employed a next generation sequencing strategy to analyse “mutation hotspots” in 50 human cancer genes. Mutations were identified for HRAS (c.37G 〉 C; p.G13R and c.182A 〉 G; p.Q61R) in 7.1% (6/85); for BRAF (c.1799T 〉 A; p.V600E) in 1.2% (1/85) of tumours; and for TP53 (c.1010G 〉 A; p.R337H) in 2.35% (2/85) of cases. Twenty-one tumours harboured mutations in inherited PCC/PGL/HNPGL genes and no HRAS, BRAF , or TP53 mutations occurred in this group. Combining our data with previous reports of HRAS mutations in PCC/PGL we find that the mean frequency of HRAS/BRAF mutations in sporadic PCC/PGL is 8.9% (24/269) and in PCC/PGL with an inherited gene mutation 0% (0/148) suggesting that HRAS/BRAF mutations and inherited PCC/PGL genes mutations might be mutually exclusive. We report the first evidence for BRAF mutations in the pathogenesis of PCC/PGL/HNPGL.
Type of Medium:
Online Resource
ISSN:
1687-8337
,
1687-8345
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2015
detail.hit.zdb_id:
2502951-4
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