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Characterization of novel genetic alterations in salivary gland secretory carcinoma.

ABSTRACT: Secretory carcinoma is a salivary gland tumor with a characteristic chromosomal translocation that results in an ETV6-NTRK3 fusion gene. Secretory carcinoma shows relatively frequent rates of lymph-node metastasis and tumor recurrence and has a characteristic histology. Except for the ETV6 translocation, genomic alterations in secretory carcinoma have not been reported. In the present study, we characterized the novel recurrent genetic mutations of secretory carcinoma. On the basis of histology, immunohistochemistry, and ETV6 gene break-apart fluorescence in situ hybridization assays, 22 tumors were classified as secretory carcinomas (19 ETV6 translocation-positive and 3 ETV6 translocation-negative secretory carcinomas) and their clinicopathologic characteristics were reviewed. Targeted deep sequencing analyses were performed on 20 secretory carcinomas (17 ETV6 translocation-positive and 3 ETV6 translocation-negative secretory carcinomas) to investigate their genetic alterations. The A16V (C?T) mutation in PRSS1, which encodes a cationic trypsinogen and has a mutation associated with hereditary pancreatitis and pancreatic adenocarcinoma, was observed in 40% (8/20) (7/17 of ETV6 translocation-positive and 1/3 of ETV6 translocation-negative secretory carcinomas). Pathogenic variants of MLH1, MUTYH, and STK11 were also identified. Variants of uncertain significance included mutations in KMT5A. These novel characteristic genetic alterations may advance current understandings of secretory carcinoma tumorigenesis and progression, leading to improved diagnoses and treatment strategies.

SUBMITTER: Na K

PROVIDER: S-EPMC7113190 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Characterization of novel genetic alterations in salivary gland secretory carcinoma.

Na Kiyong K Hernandez-Prera Juan C JC Lim Jae-Yol JY Woo Ha Young HY Yoon Sun Och SO

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20191210 4

Secretory carcinoma is a salivary gland tumor with a characteristic chromosomal translocation that results in an ETV6-NTRK3 fusion gene. Secretory carcinoma shows relatively frequent rates of lymph-node metastasis and tumor recurrence and has a characteristic histology. Except for the ETV6 translocation, genomic alterations in secretory carcinoma have not been reported. In the present study, we characterized the novel recurrent genetic mutations of secretory carcinoma. On the basis of histology, ...[more]

PMID: 31822803

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Project description:BackgroundDespite the devastating global impact of mosquito-borne illnesses on human health, very little is known about mosquito developmental biology. In this investigation, functional genetic analysis of embryonic salivary gland development was performed in Aedes aegypti, the dengue and yellow fever vector and an emerging model for vector mosquito development. Although embryonic salivary gland development has been well studied in Drosophila melanogaster, little is known about this process in mosquitoes or other arthropods.ResultsMosquitoes possess orthologs of many genes that regulate Drosophila melanogaster embryonic salivary gland development. The expression patterns of a large subset of these genes were assessed during Ae. aegypti development. These studies identified a set of molecular genetic markers for the developing mosquito salivary gland. Analysis of marker expression allowed for tracking of the progression of Ae. aegypti salivary gland development in embryos. In Drosophila, the salivary glands develop from placodes located in the ventral neuroectoderm. However, in Ae. aegypti, salivary marker genes are not expressed in placode-like patterns in the ventral neuroectoderm. Instead, marker gene expression is detected in salivary gland rudiments adjacent to the proventriculus. These observations highlighted the need for functional genetic characterization of mosquito salivary gland development. An siRNA- mediated knockdown strategy was therefore employed to investigate the role of one of the marker genes, cyclic-AMP response element binding protein A (Aae crebA), during Ae. aegypti salivary gland development. These experiments revealed that Aae crebA encodes a key transcriptional regulator of the secretory pathway in the developing Ae. aegypti salivary gland.ConclusionsThe results of this investigation indicated that the initiation of salivary gland development in Ae. aegypti significantly differs from that of D. melanogaster. Despite these differences, some elements of salivary gland development, including the ability of CrebA to regulate secretory gene expression, are conserved between the two species. These studies underscore the need for further analysis of mosquito developmental genetics and may foster comparative studies of salivary gland development in additional insect species.

Project description:ObjectivesMammary analog secretory carcinoma (MASC) is a classification of salivary gland tumors, recently included within the term secretory carcinoma. Previous descriptions of this diagnosis have largely consisted of case reports and case series with few studies investigating its clinical characteristics as compared to non-MASC tumors. Our objective was to use a large patient database to compare the clinical characteristics of mammary analog secretory carcinoma vs. non-mammary analog secretory carcinoma salivary gland tumors.MethodsThe National Cancer Database was queried between September and October 2022 for histological diagnosis of mammary analog secretory carcinoma and non-MASC salivary tumors. Patients diagnosed with mammary analog secretory carcinoma and non-mammary analog secretory carcinoma salivary tumors between the period of 2004 through 2019 were included in this analysis. Various demographic and clinical variables were abstracted from the database and compared using Wilcoxon rank sum and chi-square tests. Survival was compared between cohorts using Cox proportional hazards regression.ResultsOverall, compared to non-mammary analog secretory carcinoma diagnoses (n = 47668), mammary analog secretory carcinoma tumors (n = 384) affected younger individuals, displayed favorable pathologic staging and tumor grade, and were less likely to invade surrounding tissues. Patients with mammary analog secretory carcinoma tumors also received treatment more quickly following diagnosis compared to patients with non-mammary analog secretory carcinoma tumors. The risk of death was 4.3 times greater for non-mammary analog secretory carcinoma diagnoses when adjusted for patient variables (hazard ratio = 4.3, 95% confidence interval [2.37-7.71], p < 0.001).ConclusionsClinically, mammary analog secretory carcinoma salivary tumors have a more indolent course compared to other salivary cancers. Additional studies are needed to determine the natural history of this tumor type.

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Characterization of novel genetic alterations in salivary gland secretory carcinoma.

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Characterization of novel genetic alterations in salivary gland secretory carcinoma.

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