Dataset Information

Comparative RNA-Sequencing Analysis Benefits a Pediatric Patient With Relapsed Cancer.

ABSTRACT: Clinical detection of sequence and structural variants in known cancer genes points to viable treatment options for a minority of children with cancer.1 To increase the number of children who benefit from genomic profiling, gene expression information must be considered alongside mutations.2,3 Although high expression has been used to nominate drug targets for pediatric cancers,4,5 its utility has not been evaluated in a systematic way.6 We describe a child with a rare sarcoma that was profiled with whole-genome and RNA sequencing (RNA-Seq) techniques. Although the tumor did not harbor DNA mutations targetable by available therapies, incorporation of gene expression information derived from RNA-Seq analysis led to a therapy that produced a significant clinical response. We use this case to describe a framework for inclusion of gene expression into the clinical genomic evaluation of pediatric tumors.

SUBMITTER: Newton Y

PROVIDER: S-EPMC6675034 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Comparative RNA-Sequencing Analysis Benefits a Pediatric Patient With Relapsed Cancer.

Newton Yulia Y Rassekh S Rod SR Deyell Rebecca J RJ Shen Yaoqing Y Jones Martin R MR Dunham Chris C Yip Stephen S Leelakumari Sreeja S Zhu Jingchun J McColl Duncan D Swatloski Teresa T Salama Sofie R SR Ng Tony T Hendson Glenda G Lee Anna F AF Ma Yussanne Y Moore Richard R Mungall Andrew J AJ Haussler David D Stuart Joshua M JM Jantzen Colleen C Laskin Janessa J Jones Steven J M SJM Marra Marco A MA Morozova Olena O

JCO precision oncology 20180419

Clinical detection of sequence and structural variants in known cancer genes points to viable treatment options for a minority of children with cancer.1 To increase the number of children who benefit from genomic profiling, gene expression information must be considered alongside mutations.2,3 Although high expression has been used to nominate drug targets for pediatric cancers,4,5 its utility has not been evaluated in a systematic way.6 We describe a ...[more]

PMID: 31372595

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Project description:ImportancePediatric cancers are epigenetic diseases; therefore, considering tumor gene expression information is necessary for a complete understanding of the tumorigenic processes.ObjectiveTo evaluate the feasibility and utility of incorporating comparative gene expression information into the precision medicine framework for difficult-to-treat pediatric and young adult patients with cancer.Design, setting, and participantsThis cohort study was conducted as a consortium between the University of California, Santa Cruz (UCSC) Treehouse Childhood Cancer Initiative and clinical genomic trials. RNA sequencing (RNA-Seq) data were obtained from the following 4 clinical sites and analyzed at UCSC: British Columbia Children's Hospital (n = 31), Lucile Packard Children's Hospital at Stanford University (n = 80), CHOC Children's Hospital and Hyundai Cancer Institute (n = 46), and the Pacific Pediatric Neuro-Oncology Consortium (n = 24). The study dates were January 1, 2016, to March 22, 2017.ExposuresParticipants underwent tumor RNA-Seq profiling as part of 4 separate clinical trials at partner hospitals. The UCSC either downloaded RNA-Seq data from a partner institution for analysis in the cloud or provided a Docker pipeline that performed the same analysis at a partner institution. The UCSC then compared each participant's tumor RNA-Seq profile with more than 11 000 uniformly analyzed tumor profiles from pediatric and young adult patients with cancer, downloaded from public data repositories. These comparisons were used to identify genes and pathways that are significantly overexpressed in each patient's tumor. Results of the UCSC analysis were presented to clinical partners.Main outcomes and measuresFeasibility of a third-party institution (UCSC Treehouse Childhood Cancer Initiative) to obtain tumor RNA-Seq data from patients, conduct comparative analysis, and present analysis results to clinicians; and proportion of patients for whom comparative tumor gene expression analysis provided useful clinical and biological information.ResultsAmong 144 samples from children and young adults (median age at diagnosis, 9 years; range, 0-26 years; 72 of 118 [61.0%] male [26 patients sex unknown]) with a relapsed, refractory, or rare cancer treated on precision medicine protocols, RNA-Seq-derived gene expression was potentially useful for 99 of 144 samples (68.8%) compared with DNA mutation information that was potentially useful for only 34 of 74 samples (45.9%).Conclusions and relevanceThis study's findings suggest that tumor RNA-Seq comparisons may be feasible and highlight the potential clinical utility of incorporating such comparisons into the clinical genomic interpretation framework for difficult-to-treat pediatric and young adult patients with cancer. The study also highlights for the first time to date the potential clinical utility of harmonized publicly available genomic data sets.

Dataset Information

Comparative RNA-Sequencing Analysis Benefits a Pediatric Patient With Relapsed Cancer.

Publications

Comparative RNA-Sequencing Analysis Benefits a Pediatric Patient With Relapsed Cancer.

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