Diagnostic Value of Next-Generation Sequencing in an Unusual Sphenoid Tumor

Abstract

Extraordinary advancements in sequencing technology have made what was once a decade-long multi-institutional endeavor into a methodology with the potential for practical use in a clinical setting.We therefore set out to examine the clinical value of next-generation sequencing by enrolling patients with incurable or ambiguous tumors into the Personalized OncoGenomics initiative at the British Columbia Cancer Agency whereby whole genome and transcriptome analyses of tumor/ normal tissue pairs are completed with the ultimate goal of directing therapeutics. First, we established that the sequencing, analysis, and communication with oncologists could be completed in less than 5 weeks. Second, we found that cancer diagnostics is an area that can greatly benefit from the comprehensiveness of a whole genome analysis. Here, we present a scenario in which a metastasized sphenoid mass, which was initially thought of as an undifferentiated squamous cell carcinoma, was rediagnosed as an SMARCB1-negative rhabdoid tumor based on the newly acquired finding of homozygous SMARCB1 deletion. The new diagnosis led to a change in chemotherapy and a complete nodal response in the patient. This study also provides additional insight into the mutational landscapeof an adult SMARCB1-negative tumor that has not been explored at a whole genome and transcriptome level. The Oncologist 2014;19:623-630Implications for Practice: We show that use of next-generation sequencing in clinical settings is practical and can benefit patients because of the ability to define tumors genetically.

SMARCB1 (INI-1)-deficient Sinonasal Carcinoma

“…Although comprehensive genetic studies are still lacking, the one SMARCB1-deficient sinonasal carcinoma analyzed by next-generation sequencing failed to reveal any additional genetic aberrations other than homozygous SMARCB1 deletion. 14,29 Second, the SMARCB1 deficient sinonasal carcinomas defied classification as some other recognized tumor type and showed no evidence of high grade transformation from a preexisting well differentiated carcinoma. They consistently lack squamous differentiation, are negative for NUT, and do not harbor the oncogenic viruses HPV or EBV.…”

“…Since those initial descriptions, only two additional small series and a few case reports have been published on SMARCB1-deficient sinonasal carcinomas. 14-20, To more fully characterize the nature of this tumor type including its complete morphologic spectrum, its clinical behavior and its biology, we updated our previously reported experience and prospectively collected new cases from our own practices and from multiple other institutions.…”

Carcinoma Ex Pleomorphic Adenoma: Case Report and Options for Systemic Therapy

“…As part of an experimental protocol, a subsequent biopsy sample was analyzed by whole-genome sequencing and was compared with constitutive dna from a blood sample to identify acquired somatic mutations in this woman's tumour 3 . Transcriptome data from the same biopsy sample was compared with the compendium of 19 normal libraries of various tissue types to find overexpressed and underexpressed genes.…”

Personalized Oncogenomics in the Management of Gastrointestinal Carcinomas—Early Experiences from a Pilot Study

“…The tumour sample was compared with the normal sample to identify somatic copy-number variants [CNAseq (version 0.0. 6 15 to include alignments to a database of exon junction sequences and subsequent repositioning onto the genomic reference. The rna sequencing data were processed using the Genome Sciences Centre's wtss (whole-transcriptome shotgun sequencing) pipeline coverage analysis (version 1.1) with the "stranded" option to determine gene and exon read counts and normalized expression level.…”

“…Whole-genome sequencing (wgs) and rna sequencing provide a comprehensive catalog of somatic mutations and gene expression measurements and can be of particular use in the clinical management of molecularly complex cancers such as gi carcinomas. We and others have reported on the real-time clinical use of sequencing in the diagnosis and treatment of advanced tumours [3][4][5][6][7] .…”