Dados do Trabalho

Título

Mutational profile of salivary gland neoplasms from the intercalated duct

Introdução

Salivary gland tumors are a heterogeneous group of neoplasms of head and neck tumors. They show a wide morphological variation, especially among neoplasms with prominent or partial involvement of the myoepithelial component. Currently, there are few studies correlating histological subtypes with genetic alterations in benign and malignant salivary gland tumors or that assist in their separation. Thus, understanding the molecular basis of these lesions would be useful for differential diagnosis and classification by evaluating their mutational profiles.

Objetivo

Determination of a mutation profile in benign and malignant salivary gland neoplasms derived from the intercalated duct to check if the tumors can be classified according to the mutation profile of these genes.

Métodos

We selected 53 tumors (28 cases of pleomorphic adenoma, 03 of myoepithelioma, 07 of basal cell adenoma, 08 of carcinoma ex-pleomorphic adenoma, 04 of myoepithelial carcinoma and 03 of basal cell adenocarcinoma) that had paraffin material available. Given the rarity and genetic preservation protocol, DNA extraction was done, and 15 samples were qualified in terms of quantity and integrity before being treated with Uracil DNA glycosylase (UDG) for New Generation Sequencing (NGS). The Ion AmpliSeq Comprehensive Cancer Panel (Thermo Fisher Scientific, USA) was utilized for NGS of the DNA samples, and it includes 409 genes frequently mutated in cancer. The sequencing was performed on the Ion GeneStudio S5 Plus platform, following the manufacturer's instructions. The analysis was carried out using the Torrent Suite 5.12.3 and Varseq 2.2.5 softwares, following quality requirements. Variants affecting the protein's coding region were chosen. The alignment of the readings reporting the variant was visually examined (CEP protocol 2706/19).

Resultados

Following sequencing, 13 samples yielded excellent results: three cases of pleomorphic adenoma, two cases of myoepithelioma, two cases of basal cell adenoma, three cases of carcinoma ex-pleomorphic adenoma, two cases of myoepithelioma, and one case of basal cell adenocarcinoma. So far, missense-type alterations have been observed in 81 genes, considering all cases studied. These genes are related to cell proliferation pathways, apoptosis evasion, genomic instability, and angiogenesis maintenance.

Conclusões

Finally, in our investigation, we were able to identify changes in different genes in a group of salivary gland intercalated duct tumors. The next step involves the understanding of the relationship between the altered genes and metabolic/signaling networks, and to validate the findings.

Palavras-chave

Salivary gland tumors / NGS / Mutational profiling