Sannia Sjöstedt1, Ane Yde Schmidt2, Filipe Garrett Vieira2, Gro Linno Willemoe3, Tina Klitmøller Agander3, Caroline Olsen4, Finn Cilius Nielsen2, Christian von Buchwald5. 1. Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. sannia.mia.svenningsen.sjoestedt.01@regionh.dk. 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. 5. Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.
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.
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.
Entities:
Keywords:
Cancer; DNA sequencing; Genomics; Intestinal type adenocarcinoma; Mutations; Sinonasal
Authors: Eva Bandrés; Raquel Malumbres; Elena Cubedo; Beatriz Honorato; Ruth Zarate; Alberto Labarga; Unai Gabisu; Jesus Javier Sola; Jesus García-Foncillas Journal: Oncol Rep Date: 2007-05 Impact factor: 3.906
Authors: Montserrat Alonso-Sardón; Antonio-J Chamorro; Ignacio Hernández-García; Helena Iglesias-de-Sena; Helena Martín-Rodero; Cristian Herrera; Miguel Marcos; José Antonio Mirón-Canelo Journal: PLoS One Date: 2015-07-20 Impact factor: 3.240
Authors: Lukas E Dow; Kevin P O'Rourke; Janelle Simon; Darjus F Tschaharganeh; Johan H van Es; Hans Clevers; Scott W Lowe Journal: Cell Date: 2015-06-18 Impact factor: 41.582