Genomic Profiling of Pediatric Acute Myeloid Leukemia Reveals a Changing Mutational Landscape from Disease Diagnosis to Relapse.

TitleGenomic Profiling of Pediatric Acute Myeloid Leukemia Reveals a Changing Mutational Landscape from Disease Diagnosis to Relapse.
Publication TypeJournal Article
Year of Publication2016
AuthorsFarrar, JE, Schuback, HL, Ries, RE, Wai, D, Hampton, OA, Treviño, LR, Alonzo, TA, Auvil, JMGuidry, Davidsen, TM, Gesuwan, P, Hermida, L, Muzny, DM, Dewal, N, Rustagi, N, Lewis, LR, Gamis, AS, Wheeler, DA, Smith, MA, Gerhard, DS, Meshinchi, S
JournalCancer Res
Volume76
Issue8
Pagination2197-205
Date Published2016 Apr 15
ISSN1538-7445
Abstract

The genomic and clinical information used to develop and implement therapeutic approaches for acute myelogenous leukemia (AML) originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative used whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML. One hundred forty-five somatic variants at diagnosis (median 6 mutations/patient) and 149 variants at relapse (median 6.5 mutations) were identified and verified by orthogonal methodologies. Recurrent somatic variants [in (greater than or equal to) 2 patients] were identified for 10 genes (FLT3, NRAS, PTPN11, WT1, TET2, DHX15, DHX30, KIT, ETV6, KRAS), with variable persistence at relapse. The variant allele fraction (VAF), used to measure the prevalence of somatic mutations, varied widely at diagnosis. Mutations that persisted from diagnosis to relapse had a significantly higher diagnostic VAF compared with those that resolved at relapse (median VAF 0.43 vs. 0.24, P 0.4 persisted to relapse compared with 28% with VAF

DOI10.1158/0008-5472.CAN-15-1015
Alternate JournalCancer Res.
PubMed ID26941285
PubMed Central IDPMC4873364
Grant ListR01 CA114563 / CA / NCI NIH HHS / United States
HHSN261200800001 / RC / CCR NIH HHS / United States
U10 CA098543 / CA / NCI NIH HHS / United States
U10 CA180886 / CA / NCI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States