Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 859-865 |
| Number of pages | 7 |
| Journal | Otolaryngology - Head and Neck Surgery (United States) |
| Volume | 159 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 1 2018 |
| Externally published | Yes |
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Keywords
- NOTCH
- sinonasal SCC
- SOX4
ASJC Scopus subject areas
- Surgery
- Otorhinolaryngology
Cite this
Whole-Exome Sequencing of Sinonasal Small Cell Carcinoma Arising within a Papillary Schneiderian Carcinoma In Situ. / Smith, Joshua; Kulkarni, Aditi; Birkeland, Andrew C.; McHugh, Jonathan B.; Brenner, J. Chad.
In: Otolaryngology - Head and Neck Surgery (United States), Vol. 159, No. 5, 01.11.2018, p. 859-865.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Whole-Exome Sequencing of Sinonasal Small Cell Carcinoma Arising within a Papillary Schneiderian Carcinoma In Situ
AU - Smith, Joshua
AU - Kulkarni, Aditi
AU - Birkeland, Andrew C.
AU - McHugh, Jonathan B.
AU - Brenner, J. Chad
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - NOTCH
KW - sinonasal SCC
KW - SOX4
UR - http://www.scopus.com/inward/record.url?scp=85047426734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047426734&partnerID=8YFLogxK
U2 - 10.1177/0194599818774004
DO - 10.1177/0194599818774004
M3 - Article
C2 - 29734873
AN - SCOPUS:85047426734
VL - 159
SP - 859
EP - 865
JO - Otolaryngology - Head and Neck Surgery (United States)
JF - Otolaryngology - Head and Neck Surgery (United States)
SN - 0194-5998
IS - 5
ER -