scholarly journals Targeted Next‐Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability

2015 ◽  
Vol 36 (12) ◽  
pp. 1197-1204 ◽  
Author(s):  
Detelina Grozeva ◽  
Keren Carss ◽  
Olivera Spasic‐Boskovic ◽  
Maria‐Isabel Tejada ◽  
Jozef Gecz ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Next Generation Sequencing ◽  
Sequencing Analysis ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Next Generation Sequencing Analysis ◽  
Generation Sequencing

scholarly journals Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Andrea Luchetti ◽  
Diana Walsh ◽  
Fay Rodger ◽  
Graeme Clark ◽  
Tom Martin ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Somatic Mutations ◽  
Human Cancer ◽  
Sequencing Analysis ◽  
Cancer Genes ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Next Generation Sequencing Analysis ◽  
Sequencing Strategy ◽  
Generation Sequencing

At least 12 genes (FH, HIF2A, MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127,andVHL) 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 inHRAS, HIF2A, NF1, RET,andVHLhave 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 forHRAS(c.37G>C; p.G13R and c.182A>G; p.Q61R) in 7.1% (6/85); forBRAF(c.1799T>A; p.V600E) in 1.2% (1/85) of tumours; and forTP53(c.1010G>A; p.R337H) in 2.35% (2/85) of cases. Twenty-one tumours harboured mutations in inherited PCC/PGL/HNPGL genes and noHRAS, BRAF, orTP53mutations occurred in this group. Combining our data with previous reports ofHRASmutations in PCC/PGL we find that the mean frequency ofHRAS/BRAFmutations in sporadic PCC/PGL is 8.9% (24/269) and in PCC/PGL with an inherited gene mutation 0% (0/148) suggesting thatHRAS/BRAFmutations and inherited PCC/PGL genes mutations might be mutually exclusive. We report the first evidence forBRAFmutations in the pathogenesis of PCC/PGL/HNPGL.

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