Major driver mutations are shared between sinonasal intestinal-type adenocarcinoma and the morphologically identical col
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ORIGINAL ARTICLE – CANCER RESEARCH
Major driver mutations are shared between sinonasal intestinal‑type adenocarcinoma and the morphologically identical colorectal adenocarcinoma Sannia Sjöstedt1 · Ane Yde Schmidt2 · Filipe Garrett Vieira2 · Gro Linno Willemoe3 · Tina Klitmøller Agander3 · Caroline Olsen4 · Finn Cilius Nielsen2 · Christian von Buchwald1 Received: 8 August 2020 / Accepted: 5 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose The purpose of our study was to compare genomic changes in sinonasal intestinal-type adenocarcinoma (sITAC) and colorectal adenocarcinoma (CRC), as they are histomorphologically indistinguishable. This can cause diagnostic difficulties as sinonasal tumours initially diagnosed as sITAC may represent metastasis from CRC, a frequent cancer. Previous studies have not uncovered the underlying mechanism behind the histomorphological resemblance. Methods/patients Tissue samples from all consecutive patients with sITAC at our facility (20 patients) were compared to samples from 20 patients with CRC as well as samples from 2 patients with both CRC and sinonasal tumours. DNA sequencing was performed using Illumina TruSight Oncology 500 panel consisting of 523 cancer-associated genes. Frequent mutations were inspected manually using the Integrative Genomics Viewer. Results Several well-known cancer-associated genes were mutated in the CRC group, but also in the sinonasal ITAC group. These genes included APC mutated in 65% of the CRC group and 37% of the sinonasal ITAC group, and TP53 mutated in 65% of CRC samples and 58% of ITAC samples. These shared mutations may explain the histomorphological similarities. Successful DNA sequencing was performed on the colorectal sample from one of the two patients with both CRC and sinonasal tumour. Comparing mutations in these samples from one patient we have shown that the sinonasal tumour in all probability was a CRC metastasis. Conclusion We have identified several genetic similarities between sITAC and CRC. This discovery brings us closer to understanding mechanisms behind the development of sITAC—and hopefully in the future targeted therapy. Keywords Sinonasal · Cancer · DNA sequencing · Genomics · Mutations · Intestinal type adenocarcinoma
Introduction
* Sannia Sjöstedt [email protected] 1
Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
2
Center for Genomic Medicine, Copenhagen University Hospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
3
Department of Pathology, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
4
Department of Pathology, Zealand University Hospital Roskilde, Sygehusvej 10, 4000 Roskilde, Denmark
In the sinonasal tract (nasal cavity and paranasal sinuses), the majority of malignancies are carcinomas. Squamous cell carcinomas are most frequent, followed by adenocarcinoma; the latter subdivided into intestinal-ty
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