Aberrant expression of ALK and EZH2 in Merkel cell carcinoma

Tuukka Veija,Tom Bohling,Virinder Kaur Sarhadi,Sakari Knuutila,Virve Koljonen,Mia Kero

doi:10.1186/s12885-017-3233-5

Tuukka Veija, Tom Bohling + Show 4 more

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https://doi.org/10.1186/s12885-017-3233-5

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Journal: BMC Cancer	Publication Date: Mar 31, 2017
Citations: 20	License type: open-access

Affiliation: University of Helsinki, Helsinki University Hospital

Abstract

BackgroundDistinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC.MethodsRNA expression of 50 cancer-related genes in 26 MCC tumors was analyzed by targeted amplicon based next-generation sequencing using the Ion Torrent technology and the expression compared with that of normal, non-cancerous skin samples. Sequencing data were processed using Torrent Suite™ Software. Expression profiles of MCV-negative and MCV-positive tumors were compared. Fluorescence in situ hybridization was performed to study ALK rearrangements and immunohistochemistry to study ALK expression in tumor tissue.ResultsALK, CDKN2A, EZH2 and ERBB4 were overexpressed, and EGFR, ERBB2, PDGFRA and FGFR1 were underexpressed in MCC tumors compared to normal skin. In the MCV-negative tumors, MET, NOTCH1, FGFR3, and SMO were overexpressed and JAK3 and NPM1 were under-expressed compared to the MCV-positive tumors.ConclusionsHigh expression of ALK, CDKN2A and EZH2 was recorded in MCC tumors. No ALK fusion was seen by FISH analysis. Overexpression of EZH2 suggests its potential as a drug target in MCC.

Highlights

Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection
Overexpression of ALK, CDKN2A, EZH2 and ERBB4 was recorded in MCC samples compared with normal skin samples
Downregulation of EGFR, ERBB2, PDGFRA and FGFR1 was evident in MCC tumors compared with normal skin samples (Fig. 1)

Summary

Introduction

Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. We studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC. UV-radiation and Merkel cell polyomavirus (MCV) infection contribute to oncogenesis in MCC. [1] The viral oncogenic pathway accounts for the large majority of MCC tumors, as 80% of the tumors are MCV-positive. Clonal integration of the MCV DNA into the tumor cell genome as well as mutations in the viral Large T Antigen enable oncogenic transformation in MCV-positive MCC. Recent studies show that MCVnegative MCC tumors have a much higher mutational burden than MCV-positives. We aspired to examine the RNA expression of 50 known cancer genes in MCC tumors.

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