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  • GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation.

GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation.

American journal of human genetics (2016-08-02)
Young H Lim, Antonella Bacchiocchi, Jingyao Qiu, Robert Straub, Anna Bruckner, Lionel Bercovitch, Deepak Narayan, Jennifer McNiff, Christine Ko, Leslie Robinson-Bostom, Richard Antaya, Ruth Halaban, Keith A Choate
摘要

Vascular tumors are among the most common neoplasms in infants and children; 5%-10% of newborns present with or develop lesions within the first 3 months of life. Most are benign infantile hemangiomas that typically regress by 5 years of age; other vascular tumors include congenital tufted angiomas (TAs), kaposiform hemangioendotheliomas (KHEs), and childhood lobular capillary hemangiomas (LCHs). Some of these lesions can become locally invasive and unresponsive to pharmacologic intervention, leading to significant complications. Recent investigation has revealed that activating mutations in HRAS, KRAS, NRAS, GNAQ, and GNA11 can cause certain types of rare childhood vascular tumors, and we have now identified causal recurrent somatic activating mutations in GNA14 by whole-exome and targeted sequencing. We found somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations in one KHE, one TA, and one LCH and a GNA11 c.547C>T (p.Arg183Cys) mutation in two LCH lesions. We examined mutation pathobiology via expression of mutant GNA14 or GNA11 in primary human endothelial cells and melanocytes. GNA14 and GNA11 mutations induced changes in cellular morphology and rendered cells growth-factor independent by upregulating the MAPK pathway. Our findings identify GNA14 mutations as a cause of childhood vascular tumors, offer insight into mechanisms of oncogenic transformation by mutations affecting Gaq family members, and identify potential targets for therapeutic intervention.

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抗 β-肌动蛋白抗体,小鼠单克隆, clone AC-15, purified from hybridoma cell culture
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抗 α-微管蛋白单克隆抗体 小鼠抗, clone B-5-1-2, ascites fluid
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单克隆抗 KRAS 小鼠抗, clone 3B10-2F2, purified immunoglobulin, buffered aqueous solution