Novel somatic mutations in heterotrimeric G proteins in melanoma

Why does melanoma metastasize into the brain? Genes with pleiotropic effects might be the key

“…The detected rs208353 SNP is located in the intron region of the GNA12 gene (synonyms: GNA 12 | MGC104623 | MGC99644 | NNX3 | RMP | gep), which encodes guanine nucleotide binding protein (G protein) alpha 12. This finding supports recent result of Cardenas-Navia et al (2010) who found that GNA12 and six other G-protein genes are frequently mutated in melanoma (somatic mutations). The literature review showed that the GNA12 gene plays a critical role in regulating TJ, which in turn is an essential component of the BBB permeability.…”

Somatic mutations in GNAQ in amelanotic/hypomelanotic blue nevi

“…Although the site of the primary was not delineated in any of these samples, none was a GNAQ mutation, lending credence to the observation that GNAQ is a critical cancer gene in BN and uveal melanoma, but not in MM [7,22]. Despite the obvious limitation of a small number of cases, the presence of GNAQ mutations in the ABN indicates that mechanisms underlying pigment homeostasis in this variant appear to be similar to those of its melanotic counterparts, although it is not quite clear why activation of the q class of the G-protein α subunit should cause an abundance of dermal pigment in one variant and not in another.…”

“…More recently, nonsynonymous, somatic mutations in a G-protein subunit have been reportedly detected in up to 17% of MM samples [22]. Although the site of the primary was not delineated in any of these samples, none was a GNAQ mutation, lending credence to the observation that GNAQ is a critical cancer gene in BN and uveal melanoma, but not in MM [7,22].…”

Gene Copy-Number Polymorphism Caused by Retrotransposition in Humans

“…This retrocopy also exhibited a similar reduction in nucleotide diversity in the Asian subpopulation, although this pattern was not significant by our test ( P  = 0.099; Figure S3). GNG10 , which has been associated with melanoma [58], has a retrocopy that forms a sense-sense pair with SBF2 , which has been implicated in Charcot-Marie-Tooth disease [59]. To gain further confidence in these results, we compared the π der /π anc ratios observed for these candidates to those calculated from random regions flanking SNPs with similar derived allele frequencies, finding that relatively few SNPs in the human genome exhibited lower π der /π anc ratios than these retroCNVs, even though some of these loci are likely themselves under positive selection.…”