Open AccessWhole‐Exome Sequencing of Sinonasal Small Cell Carcinoma Arising within a Papillary Schneiderian Carcinoma In Situ
Author(s) -
Smith Joshua,
Kulkarni Aditi,
Birkeland Andrew C.,
McHugh Jonathan B.,
Brenner J. Chad
Publication year - 2018
Publication title -
otolaryngology–head and neck surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.232
H-Index - 121
eISSN - 1097-6817
pISSN - 0194-5998
DOI - 10.1177/0194599818774004
Subject(s) - exome sequencing , biology , exome , cancer research , cdkn2a , carcinoma , head and neck squamous cell carcinoma , cancer , pathology , mutation , genetics , medicine , head and neck cancer , gene
Objective The pathogenetic underpinnings of extrapulmonary small cell carcinomas (EPSCCs) of the head and neck are poorly understood. We sought to describe the clinical case and whole‐exome DNA sequencing data of a patient with sinonasal Schneiderian carcinoma in situ whose tumor progressed to small cell carcinoma (SCC). Study Design Case report and whole‐exome sequencing of tumor DNA. Setting Academic medical center. Subjects and Methods A 52‐year‐old man with sinonasal Schneiderian carcinoma in situ whose tumor progressed to small cell carcinoma. We performed whole‐exome genetic sequencing and copy‐number variation (CNV) analysis of tumor and normal DNA extracted from flash‐frozen, paraffin‐embedded (FFPE) samples. Results A total of 93 high‐confidence, nonsynonymous somatic mutation events were identified in sinonasal SCC, including loss‐of‐function mutations in TP53, MAML3 , a transcriptional coactivator of the Notch pathway, and GAS6 , an activating ligand of the TAM family of tyrosine kinase receptors. Focal amplifications of chromosomal regions 6p25‐11.1, containing SOX4 and VEGFA , and 14q32.1‐32.3, containing AKT1 and the Notch inhibitory ligand DLK1 , were also seen. Further CNV analysis revealed deletions in the critical cell cycle regulators CDKN2A, RB1, RBL1 , and RBL2 and the chromatin modifier EP300 . Conclusions Small cell carcinoma may rarely arise from sinonasal Schneiderian carcinoma in situ and exhibits similar genomic aberrations (eg, SOX amplification, Notch pathway inactivation) to pulmonary small cell carcinoma.