Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
JAMA. 2011 Apr 20;305(15):1577-84. doi: 10.1001/jama.2011.497.

Use of whole-genome sequencing to diagnose a cryptic fusion oncogene.

Author information

  • 1Department of Medicine, Washington University, St Louis, Missouri, USA.

Abstract

CONTEXT:

Whole-genome sequencing is becoming increasingly available for research purposes, but it has not yet been routinely used for clinical diagnosis.

OBJECTIVE:

To determine whether whole-genome sequencing can identify cryptic, actionable mutations in a clinically relevant time frame.

DESIGN, SETTING, AND PATIENT:

We were referred a difficult diagnostic case of acute promyelocytic leukemia with no pathogenic X-RARA fusion identified by routine metaphase cytogenetics or interphase fluorescence in situ hybridization (FISH). The case patient was enrolled in an institutional review board-approved protocol, with consent specifically tailored to the implications of whole-genome sequencing. The protocol uses a "movable firewall" that maintains patient anonymity within the entire research team but allows the research team to communicate medically relevant information to the treating physician.

MAIN OUTCOME MEASURES:

Clinical relevance of whole-genome sequencing and time to communicate validated results to the treating physician.

RESULTS:

Massively parallel paired-end sequencing allowed identification of a cytogenetically cryptic event: a 77-kilobase segment from chromosome 15 was inserted en bloc into the second intron of the RARA gene on chromosome 17, resulting in a classic bcr3 PML-RARA fusion gene. Reverse transcription polymerase chain reaction sequencing subsequently validated the expression of the fusion transcript. Novel FISH probes identified 2 additional cases of t(15;17)-negative acute promyelocytic leukemia that had cytogenetically invisible insertions. Whole-genome sequencing and validation were completed in 7 weeks and changed the treatment plan for the patient.

CONCLUSION:

Whole-genome sequencing can identify cytogenetically invisible oncogenes in a clinically relevant time frame.

Comment in

PMID:
21505136
[PubMed - indexed for MEDLINE]
PMCID:
PMC3156695
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1
Figure 2
Figure 3
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Write to the Help Desk