Journal Article

Paired Tumor and Normal Whole Genome Sequencing of Metastatic Olfactory Neuroblastoma

Metpally, Raghu, Christoforides, Alexis, Arora, Shilpi, Craig, David W., Hostetter, Galen, Von Hoff, Daniel D., Tembe, Waibhav D., Carpten, John D., Liang, Winnie S., Phillips, Lori, Raju, Robert N., Kurdoglu, Ahmet, Izatt, Tyler, Baker, Angela S., Cherni, Irene, Weiss, Glen J., Sinari, Shripad

2012

Overview

Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal tract with little molecular characterization. We performed whole genome sequencing (WGS) on paired normal and tumor DNA from a patient with metastatic-ONB to identify the somatic alterations that might be drivers of tumorigenesis and/or metastatic progression. Genomic DNA was isolated from fresh frozen tissue from a metastatic lesion and whole blood, followed by WGS at >30X depth, alignment and mapping, and mutation analyses. Sanger sequencing was used to confirm selected mutations. Sixty-two somatic short nucleotide variants (SNVs) and five deletions were identified inside coding regions, each causing a non-synonymous DNA sequence change. We selected seven SNVs and validated them by Sanger sequencing. In the metastatic ONB samples collected several months prior to WGS, all seven mutations were present. However, in the original surgical resection specimen (prior to evidence of metastatic disease), mutations in KDR, MYC, SIN3B, and NLRC4 genes were not present, suggesting that these were acquired with disease progression and/or as a result of post-treatment effects. This work provides insight into the evolution of ONB cancer cells and provides a window into the more complex factors, including tumor clonality and multiple driver mutations.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Analysis / Apoptosis / Base Sequence / Bioinformatics / Biology / Cancer / Cancer metastasis / Cancer therapies / Chemotherapy / Clinical trials / Coding / Collaboration / Deoxyribonucleic acid / Development and progression / DNA / DNA Copy Number Variations / DNA sequencing / Esthesioneuroblastoma, Olfactory - genetics / Gene Library / Gene mapping / Gene sequencing / Genes / Genes, Neoplasm - genetics / Genetic aspects / Genetic Variation / Genome - genetics / Genomes / Genomics / Hematology / Humans / Kinases / Lymphoma / Lymphomas / Male / Medical prognosis / Medical research / Medicine / Metastases / Metastasis / Microscopy / Molecular Sequence Data / Mutation / Mutation - genetics / Myc protein / Nasal Cavity / Neoplasm Metastasis - genetics / Neuroblastoma / Nose Neoplasms - genetics / Nucleotide sequence / Pediatrics / Polymorphism, Single Nucleotide / Sequence Analysis, DNA / Studies / Surgery / Tumorigenesis / Tumors