Clinical targeted exome-based sequencing in combination with genome-wide copy number profiling: precision medicine analysis of 203 pediatric brain tumors.

Ramkissoon SH1, Bandopadhayay P1, Hwang J1, Ramkissoon LA1, Greenwald NF1, Schumacher SE1, O'Rourke R1, Pinches N1, Ho P1, Malkin H1, Sinai C1, Filbin M1, Plant A1, Bi WL1, Chang MS1, Yang E1, Wright KD1, Manley PE1, Ducar M1, Alexandrescu S1, Lidov H1, Delalle I1, Goumnerova LC1, Church AJ1, Janeway KA1, Harris MH1, MacConaill LE1, Folkerth RD1, Lindeman NI1, Stiles CD1, Kieran MW1, Ligon AH1, Santagata S1, Dubuc AM1, Chi SN2, Beroukhim R2, Ligon KL2.

Author information

Abstract

BACKGROUND:

Clinical genomics platforms are needed to identify targetable alterations, but implementation of these technologies and best practices in routine clinical pediatric oncology practice are not yet well established.

METHODS:

Profile is an institution-wide prospective clinical research initiative that uses targeted sequencing to identify targetable alterations in tumors. OncoPanel, a multiplexed targeted exome-sequencing platform that includes 300 cancer-causing genes, was used to assess single nucleotide variants and rearrangements/indels. Alterations were annotated (Tiers 1-4) based on clinical significance, with Tier 1 alterations having well-established clinical utility. OncoCopy, a clinical genome-wide array comparative genomic hybridization (aCGH) assay, was also performed to evaluate copy number alterations and better define rearrangement breakpoints.

RESULTS:

Cancer genomes of 203 pediatric brain tumors were profiled across histological subtypes, including 117 samples analyzed by OncoPanel, 146 by OncoCopy, and 60 tumors subjected to both methodologies. OncoPanel revealed clinically relevant alterations in 56% of patients (44 cancer mutations and 20 rearrangements), including BRAF alterations that directed the use of targeted inhibitors. Rearrangements in MYB-QKI, MYBL1, BRAF, and FGFR1 were also detected. Furthermore, while copy number profiles differed across histologies, the combined use of OncoPanel and OncoCopy identified subgroup-specific alterations in 89% (17/19) of medulloblastomas.

CONCLUSION:

The combination of OncoPanel and OncoCopy multiplex genomic assays can identify critical diagnostic, prognostic, and treatment-relevant alterations and represents an effective precision medicine approach for clinical evaluation of pediatric brain tumors.

KEYWORDS:

array CGH; brain tumor; clinical sequencing; pediatric neuro-oncology; precision medicine

PMID:: 28104717
DOI:: 10.1093/neuonc/now294

[PubMed - as supplied by publisher]

From HuGE Literature Finder Database

This database contains published literature on genetic associations and other human genome epidemiology

Clinical targeted exome-based sequencing in combination with genome-wide copy number profiling: precision medicine analysis of 203 pediatric brain tumors.
Neuro-oncology 2017 Jan .
Ramkissoon Shakti H, Bandopadhayay Pratiti, Hwang Jaeho, Ramkissoon Lori A, Greenwald Noah F, Schumacher Steven E, O'Rourke Ryan, Pinches Nathan, Ho Patricia, Malkin Hayley, Sinai Claire, Filbin Mariella, Plant Ashley, Bi Wenya Linda, Chang Michael S, Yang Edward, Wright Karen D, Manley Peter E, Ducar Matthew, Alexandrescu Sanda, Lidov Hart, Delalle Ivana, Goumnerova Liliana C, Church Alanna J, Janeway Katherine A, Harris Marian H, MacConaill Laura E, Folkerth Rebecca D, Lindeman Neal I, Stiles Charles D, Kieran Mark W, Ligon Azra H, Santagata Sandro, Dubuc Adrian M, Chi Susan N, Beroukhim Rameen, Ligon Keith
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