Universität zu Köln

Hieggelke, Lena, Heydt, Carina, Castiglione, Roberta ORCID: 0000-0002-9828-4405, Rehker, Jan, Merkelbach-Bruse, Sabine, Riobello, Cristina, Llorente, Jose Luis, Hermsen, Mario A. and Buettner, Reinhard (2021). Mismatch Repair Deficiency and Somatic Mutations in Human Sinonasal Tumors. Cancers, 13 (23). BASEL: MDPI. ISSN 2072-6694

Full text not available from this repository.

Abstract

Simple Summary Sinonasal carcinomas are rare tumors with an overall poor prognosis. Due to limitations in local therapeutic approaches, systemic neo-adjuvant or adjuvant therapies are becoming increasingly important in order to improve patient outcome. This study aimed to examine potentially therapeutic targetable molecular alterations in different sinonasal tumors, including deficiency in mismatch repair proteins and microsatellite instability as well as driver mutations. According to our results, immunohistochemical (IHC) analysis of mismatch repair (MMR) proteins and sequencing-based panel analysis should be integrated into the diagnostics of clinically aggressive inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) in order to enable the therapeutic possibility of a targeted therapy. Due to limitations in local therapy approaches for sinonasal tumors, improvement in systemic therapies plays a pivotal role for prolongation of the patient's survival. The aim of this study was to examine potential biomarkers, including deficiency in mismatch repair proteins (dMMR)/microsatellite instability (MSI-H) in sinonasal cancers and their precancerous lesions. A comprehensive analysis of 10 sinonasal cancer cell lines by whole exome sequencing, screening 174 sinonasal tumors by immunohistochemistry (IHC) for mismatch repair deficiency and next generation sequencing (NGS) of 136 tumor samples revealed a dMMR/MSI-H sinonasal squamous cell carcinoma (SNSCC) cell line based on a somatic missense mutation in MLH1 and an overall frequency of dMMR/MSI-H SNSCC of 3.2% (4/125). Targetable EGFR mutations were found in 89.3% (25/28) of inverted sinonasal papilloma (ISP) and in 60% (6/10) of ISP-associated carcinomas. While PIK3CA and EGFR mutations were not mutually exclusive, KRAS mutated tumors were an EGFR-wildtype. The effect of potential driver mutations in FGFR2, FGFR3, BRAF, HRAS, MAP2K1, PTEN, NOTCH1 and CARD11 need further investigation. Our results suggest that biomarker testing, including MMR-IHC and NGS panel analysis, should be integrated into the diagnostics of clinically aggressive ISPs and SNSCC to assess prognosis and facilitate therapeutic decisions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hieggelke, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Castiglione, Roberta UNSPECIFIED orcid.org/0000-0002-9828-4405 UNSPECIFIED Rehker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Riobello, Cristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Llorente, Jose Luis UNSPECIFIED UNSPECIFIED UNSPECIFIED Hermsen, Mario A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-590773
DOI:	10.3390/cancers13236081
Journal or Publication Title:	Cancers
Volume:	13
Number:	23
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SQUAMOUS-CELL-CARCINOMA; PAPILLOMAVIRUS-RELATED CARCINOMA; CYSTIC-LIKE FEATURES; MICROSATELLITE INSTABILITY; CARD11 MUTATIONS; EGFR MUTATIONS; HPV INFECTION; CANCER; HEAD; EXPRESSION Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59077