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Biol."],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Clinical studies and genetic analyses have revealed that juvenile myelomonocytic leukemia (JMML) is caused by somatic and\/or germline mutations of genes involved in the RAS\/MAPK signalling pathway. Given the vastly different clinical prognosis among individual patients that have had this disease, mutations in genes of other pathways may be involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we conducted whole\u2010exome and cancer\u2010panel sequencing analyses on a bone marrow sample from a 2\u2010year old juvenile myelomonocytic leukemia patient. We also measured the microRNA profile of the same patient\u2019s bone marrow sample and the results were compared with the normal mature monocytic cells from the pooled peripheral blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified additional novel mutations in the PI3K\/AKT pathway and verified with a cancer panel targeted sequencing. We have confirmed the previously tested <jats:italic>PTPN11<\/jats:italic> gene mutation (exon 3 181G&gt;T) in the same sample and identified new nonsynonymous mutations in <jats:italic>NTRK1<\/jats:italic>, <jats:italic>HMGA2<\/jats:italic>, <jats:italic>MLH3<\/jats:italic>, <jats:italic>MYH9<\/jats:italic> and <jats:italic>AKT1<\/jats:italic> genes. Many of the microRNAs found to be differentially expressed are known to act as oncogenic MicroRNAs (onco\u2010MicroRNAs or oncomiRs), whose target genes are enriched in the PI3K\/AKT signalling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study suggests an alternative mechanism for JMML pathogenesis in addition to RAS\/MAPK pathway. This discovery may provide new genetic markers for diagnosis and new therapeutic targets for JMML patients in the future.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s40484-017-0125-2","type":"journal-article","created":{"date-parts":[[2018,1,16]],"date-time":"2018-01-16T03:36:08Z","timestamp":1516073768000},"page":"85-97","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Whole\u2010exome sequencing and microRNA profiling reveal PI3K\/AKT pathway\u2019s involvement in juvenile myelomonocytic leukemia"],"prefix":"10.1002","volume":"6","author":[{"given":"Saad M","family":"Khan","sequence":"first","affiliation":[{"name":"<!--1--> Informatics Institute and C. S. 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