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Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients.

ABSTRACT: BACKGROUND:The aggressive biology of cancers arising in adolescent and young adult (AYA; ages 15-39 years) patients is thought to contribute to poor survival outcomes. METHODS:We used clinical next-generation sequencing (NGS) results to examine the molecular alterations and diverse biology of cancer in AYA patients referred to the Phase 1 program at UT MD Anderson Cancer Center. RESULTS:Among the 28 patients analyzed (14 female and 14 male), 12 had pediatric-type cancers, six had adult-type cancers, and ten had orphan cancers. Unique, hitherto unreported aberrations were identified in all types of cancers. Aberrations in TP53, NKX2-1, KRAS, CDKN2A, MDM4, MCL1, MYC, BCL2L2, and RB1 were demonstrated across all tumor types. Five patients harbored TP53 aberrations; three patients harbored MYC, MCL1, and CDKN2A aberrations; and two patients harbored NKX2-1, KRAS, MDM4, BCL2L2, and RB1 alterations. Several patients had multiple aberrations; a patient with wild-type gastrointestinal stromal tumor harbored five alterations (MDM4, MCL1, KIT, AKT3, and PDGRFA). CONCLUSIONS:This preliminary report of NGS of cancer in AYA patients reveals diverse and unique aberrations. Further molecular profiling and a deeper understanding of the biology of these unique aberrations are warranted and may lead to targeted therapeutic interventions.

SUBMITTER: Subbiah V

PROVIDER: S-EPMC4549362 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients.

Subbiah Vivek V Bupathi Manojkumar M Kato Shumei S Livingston Andrew A Slopis John J Anderson Pete M PM Hong David S DS

Oncoscience 20150708 7

<h4>Background</h4>The aggressive biology of cancers arising in adolescent and young adult (AYA; ages 15-39 years) patients is thought to contribute to poor survival outcomes.<h4>Methods</h4>We used clinical next-generation sequencing (NGS) results to examine the molecular alterations and diverse biology of cancer in AYA patients referred to the Phase 1 program at UT MD Anderson Cancer Center.<h4>Results</h4>Among the 28 patients analyzed (14 female and 14 male), 12 had pediatric-type cancers, s ...[more]

PMID: 26328274

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Project description:Molecular technologies have allowed laboratories to detect and establish the profiles of human cancers by identifying a variety of somatic variants. In order to improve personalized patient care, we have established a next-generation sequencing (NGS) test to screen for somatic variants in primary or advanced cancers. In this study, we describe the laboratory quality management program for NGS testing, and also provide an overview of the somatic variants identified in over 1000 patient samples as well as their implications in clinical practice.Over the past one-and-a-half years, our laboratory received a total of 1028 formalin-fixed, paraffin-embedded (FFPE) tumor tissues, which consisted of non-small-cell lung carcinomas (NSCLCs), colon adenocarcinomas, glioma/glioblastomas, melanomas, breast carcinomas, and other tumor types. During this time period, we implemented a series of quality control (QC) checks that included (1) pre-DNA extraction, (2) DNA quantification, (3) DNA quality, (4) library quantification, (5) post-emulsification PCR, and (6) post-sequencing metrics. At least 10 ng of genomic DNA (gDNA) were used to prepare barcoded libraries using the AmpliSeq CHPv2. Samples were multiplexed and sequenced on Ion Torrent 318 chips using the Ion PGM System. Variants were identified using the Variant Caller Plugin, and annotation and functional predictions were performed using the Golden Helix SVS.A total of 1005 samples passed QC1-3, and following additional library preparation QC checkpoints, 877 samples were sequenced. Samples were classified into two categories: wild-type (127) and positive for somatic variants (750). Somatic variants were classified into clinically actionable (60%) and non-actionable (40%).The use of NGS in routine clinical laboratory practice allowed for the detection of tumor profiles that are essential for the selection of targeted therapies and identification of applicable clinical trials, contributing to the improvement of personalized patient care in oncology.

Dataset Information

Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients.

Publications

Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients.

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