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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

5538 - Molecular analysis of NRAS, BRAF, C-KIT, ROS1, ALK and RET alterations in serial biopsies in sinonasal mucosal melanoma

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Targeted Therapy;  Pathology/Molecular Biology

Tumour Site

Melanoma

Presenters

Georgia Anguera Palacios

Citation

Annals of Oncology (2018) 29 (suppl_8): viii372-viii399. 10.1093/annonc/mdy287

Authors

G. Anguera Palacios1, L.P. del Carpio1, M. Molina2, C. Aguado2, J.R. Gras-Cabrerizo3, X. Leon3, M. Gonzalez-Cao4, N. Karachaliou5, A. Mozos6, A. Gonzalez6, A. Barnadas1, R. Rosell4, M. Majem1

Author affiliations

  • 1 Oncology Department, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, 8026 - Barcelona/ES
  • 2 Quirón Dexeus University Hospital, Pangaea Biotech S.L., Barcelona/ES
  • 3 Otolaryngology / Head And Neck Surgery, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, 8026 - Barcelona/ES
  • 4 Instituto Oncológico Dr Rosell, Hospital Universitario Quirón Dexeus, 08028 - Barcelona/ES
  • 5 University Hospital Sagrat Cor, Institute of Oncology Rosell, Barcelona/ES
  • 6 Department Of Pathology, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, 8026 - Barcelona/ES

Resources

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Abstract 5538

Background

Sinonasal mucosal melanoma (SNMM) is a rare entity with no specific treatment. Little is known about SNMM molecular profile, a low rate of genetic alterations has been describe compared to cutaneous melanoma. We aimed to screen for several genetic alterations in SNMM.

Methods

From 1988 to 2017, we collected 20 formalin-fixed paraffin primary tumors blocks from SNMM patients and 12 local recurrences and/or distant metastasis from the same patients. We analyzed the spectrum of mutations in KIT gene (exon 9, 11 13 and 17) by standard PCR followed by Sanger sequencing, NRAS gene (exon 2, 3 and 4) by pyrosequencing and BRAF gene (exon 15) by Taqman PCR. Finally, RET, ALK and ROS1 fusions and gene expression levels were determined by nCounter.

Results

We identified gene mutations in 6/20 cases (30%). We found 2 cases (10%) with mutations in NRAS gene (both in exon 2: G12V), 3 cases (15%) with mutations in KIT (all in the exon 11: R586K, G565R, M552I) and 1 case (5%) with KRAS mutation (G12A). No BRAF mutations were detected. Interestingly, we found discrepancies in the NRAS mutational status of tumor samples obtained from 2 patients. In the first case, at diagnosis, we identified the NRAS mutation in 1 of 2 samples, and in 2 of 3 samples at the time of local recurrence. In the second case, the NRAS mutation was present at diagnosis but only in 2 of 4 samples of distant recurrence. Finally, nCounter did not reveal RET, ALK no ROS1 gene fusions or mRNA overexpression in any sample.

Conclusions

In our series of SNMM, we have found mutations in 6/20 tumors (30%) in KIT, NRAS and KRAS genes. No fusions or overexpression were found for ALK, ROS1 or RET genes. To our knowledge, this is the first reported study on these genes. We plan to further characterize this orphan population by analyzing immune-related genes.

Clinical trial identification

Legal entity responsible for the study

Georgia Anguera.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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