Genetic mutation analysis of the malignant transformation of sinonasal inverted papilloma by targeted amplicon sequencing

Shinichiro Yasukawa; Satoshi Kano; Hiromitsu Hatakeyama; Yuji Nakamaru; Dai Takagi; Takatsugu Mizumachi; Masanobu Suzuki; Takayoshi Suzuki; Akira Nakazono; Shinya Tanaka; Hiroshi Nishihara; Akihiro Homma

doi:10.1007/s10147-018-1296-1

Genetic mutation analysis of the malignant transformation of sinonasal inverted papilloma by targeted amplicon sequencing

Int J Clin Oncol. 2018 Oct;23(5):835-843. doi: 10.1007/s10147-018-1296-1. Epub 2018 May 19.

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
² Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan. skano@med.hokudai.ac.jp.
³ Department of Otolaryngology, Yokohama City University Medical Center, Yokohama, Japan.
⁴ Department of Cancer Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
⁵ Department of Cancer Center, Keio University Hospital, Tokyo, Japan.

PMID: 29779136
DOI: 10.1007/s10147-018-1296-1

Abstract

Background: The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated.

Methods: To clarify the genes responsible for the malignant transformation, we analyzed 10 cases of IP, 8 of IP with dysplasia, and 11 of squamous cell carcinoma (SCC) by targeted amplicon sequencing.

Results: The number of mutant genes increased in the order of IP < dysplasia < SCC. Significant differences were observed in the mutation rates of three genes (KRAS, APC and STK11) in particular. TP53 was altered frequently in each group and might be involved in malignant transformation based on to the site of the mutation. A comparison of the genetic variants by region of IP tissue among patients with IP alone, and those with dysplasia or SCC revealed significant differences in the mutation rate of the KRAS gene.

Conclusion: Identification of genetic mutations in KRAS is effective for predicting the malignant transformation of IP.

Keywords: Inverted papilloma; Malignant transformation; NGS; Squamous cell carcinoma; Targeted amplicon sequence.

MeSH terms

Adult
Aged
Biomarkers, Tumor / genetics*
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / pathology
Cell Transformation, Neoplastic / pathology*
DNA Mutational Analysis
Female
Humans
Male
Middle Aged
Mutation*
Nose Neoplasms / genetics*
Nose Neoplasms / pathology
Papilloma, Inverted / genetics*
Papilloma, Inverted / pathology
Paranasal Sinus Neoplasms / genetics*
Paranasal Sinus Neoplasms / pathology
Prognosis

Substances

Biomarkers, Tumor