Paired tumor and normal whole genome sequencing of metastatic olfactory neuroblastoma.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare (VGPCC), Scottsdale, Arizona, United States of America. gweiss@tgen.org
Glen J
GJ
Weiss
Winnie S
WS
Liang
Tyler
T
Izatt
Shilpi
S
Arora
Irene
I
Cherni
Robert N
RN
Raju
Galen
G
Hostetter
Ahmet
A
Kurdoglu
Alexis
A
Christoforides
Shripad
S
Sinari
Angela S
AS
Baker
Raghu
R
Metpally
Waibhav D
WD
Tembe
Lori
L
Phillips
Daniel D
DD
Von Hoff
David W
DW
Craig
John D
JD
Carpten
D000328:Adult; D001483:Base Sequence; D056915:DNA Copy Number Variations; D018304:Esthesioneuroblastoma, Olfactory / Q000235:genetics*; D015723:Gene Library; D052138:Genes, Neoplasm / Q000235:genetics; D014644:Genetic Variation; D016678:Genome / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009296:Nasal Cavity; D009362:Neoplasm Metastasis / Q000235:genetics*; D009669:Nose Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA