Intrduction

Although tumor genomic profiling has become the standard of care in oncology, this testing may not produce actionable findings in many tumors, particularly for pediatric and hard to treat cancers. These tumors simply do not harbor actionable DNA aberrations using 30-150 commonly-used cancer genes in tumor profile testing.

RNA sequencing, particularly when combined with whole exome sequencing, increases the number of actionable aberrations detected in these tumors, and may provide additional clinical utilities especially for childhood cancer patients.

Test Findings

• Whole exome analysis comprehensively characterizes tumor driver mutations using a tumor-normal comparison methodologies

• Exome-wide analysis also comprehensively characterizes germline cancer mutations

• RNA sequencing identifies gene expression signatures, fusion genes and mutational profiles at the transcriptome level

  • Pinpoints variants that regulate cancer gene expressions

  • Profiles gene fusions arising from chromosomal translocations

• This approach is complementary to routine tumor profile testing by providing additional therapy candidates and clinical outcome predictions

Benefits of RNA and Whole Exome Sequencing

Improve Clinical Outcome Prediction And Cancer Prognosis

• Fusion genes are a major cause of cancer. These are hybrid genes that usually arise from chromosomal rearrangements where two different genes were placed together, such as translocation, interstitial deletion and chromosomal insertion. Collectively, fusion genes account for approximately 20% of human cancer morbidity. Identifying fusion genes in tumors provides opportunities for targeted treatment

• RNA sequencing determines gene expression, point mutations and small indels. The analysis supports tumor classification and progression prediction. The analysis results also support predictions on how a patient will respond to specific treatments.

• Tumor driver mutations can be more comprehensively detected when whole exome data on both tumor and normal tissues is available and compared directly.

Clinical Utilities

• Obtain actionable findings in relapsed or refractory tumors, including gene fusions with a known or suspected role in tumorigenesis identified through RNA sequencing analysis

• Determine actionable findings that include overexpressions of druggable oncogenes

  • Options for patients whose tumors exhibited oncogene overexpression to be placed on targeted therapies against these alterations

• Identify additional therapeutic targets

Test Descriptions

• The test is performed at a CLIA-certified and CAP-accredited laboratory

• RNA sequencing is performed on tumor samples obtained from unstained slides of a tumor block and adjacent normal tissues

• Deep whole exome sequencing is performed on tumor samples obtained from unstained slides of a tumor block and also from a blood sample of the patient

• Gene expression, fusion gene analysis, and exome-wide tumor driver and germline mutation analysis are performed

• Clinical report is reviewed and signed by a board-certified a medical director

• Turnaround time is 1.5 months or less

Genetic Counseling Included

• Genetic counseling provided by a board-eligible genetic counselor is included