Non‐random chromosome rearrangements in adenoid cystic carcinoma of the salivary glands

Nordkvist, Anders; Mark, Joachim; Gustafsson, H.; Bang, Gisle; Stenman, Göran

doi:10.1002/gcc.2870100206

Cited by 134 publications

(79 citation statements)

References 14 publications

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“…Primary cultures were established from fresh, unfixed tumor specimens of 6 ACCs (ACC1-2 and -4 -7) as previously described (3,30). Chromosome preparations were made from primary cultures or early-passage cells.…”

Section: Methodsmentioning

confidence: 99%

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Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck

Persson

Andrén

Mark

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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639

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The transcription factor gene MYB was identified recently as an oncogene that is rearranged/duplicated in some human leukemias. Here we describe a new mechanism of activation of MYB in human cancer involving gene fusion. We show that the t(6;9)(q22-23;p23-24) translocation in adenoid cystic carcinomas (ACC) of the breast and head and neck consistently results in fusions encoding chimeric transcripts predominantly consisting of MYB exon 14 linked to the last coding exon(s) of NFIB. The minimal common part of MYB deleted as the result of fusion was exon 15 including the 3 -UTR, which contains several highly conserved target sites for miR-15a/16 and miR-150 microRNAs. These microRNAs recently were shown to regulate MYB expression negatively. We suggest that deletion of these target sites may disrupt repression of MYB leading to overexpression of MYB-NFIB transcripts and protein and to activation of critical MYB targets, including genes associated with apoptosis, cell cycle control, cell growth/angiogenesis, and cell adhesion. Forced overexpression of miR-15a/16 and miR-150 in primary fusion-positive ACC cells did not significantly alter the expression of MYB as compared with leukemic cells with MYB activation/duplication. Our data indicate that the MYB-NFIB fusion is a hallmark of ACC and that deregulation of the expression of MYB and its target genes is a key oncogenic event in the pathogenesis of ACC. Our findings also suggest that the gain-offunction activity resulting from the MYB-NFIB fusion is a candidate therapeutic target.chromosome translocation ͉ fusion oncogene ͉ miRNA ͉ adenoid cystic carcinoma F usion genes are potent oncogenes resulting from chromosome rearrangements, in particular translocations. Most fusion genes identified thus far have been in hematological disorders and mesenchymal neoplasms, and only a few have been found in carcinomas (1). This paucity probably results from an inability to discover these rearrangements rather than from a true lack of such genes in carcinomas. The recent discovery that the majority of prostate cancers harbor ETS gene fusions (2) is in line with this reasoning. Finding as yet unidentified fusion oncogenes in other carcinomas could provide important insights into the molecular pathogenesis of these cancers and also might facilitate the development of new targeted therapies.We previously have identified a recurrent and tumor-specific t(6;9)(q22-23;p23-24) translocation in adenoid cystic carcinoma (ACC) of the head and neck (3). The translocation has been found as the sole cytogenetic anomaly in several cases, indicating that it is a primary rearrangement in this carcinoma.ACC has been known as a histologically distinctive neoplasm for nearly 150 years. It is among the most common carcinomas of the salivary glands (4) but also may arise in other exocrine glands, such as in the breast, and in the cervix, vulva, and tracheobronchial tree (5). ACC usually is an aggressive, although slowly growing, cancer with a long-term poor prognosis. Most patients (80-90%) with ACC ...

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Section: Methodsmentioning

confidence: 99%

“…We previously have identified a recurrent and tumor-specific t(6;9)(q22-23;p23-24) translocation in adenoid cystic carcinoma (ACC) of the head and neck (3). The translocation has been found as the sole cytogenetic anomaly in several cases, indicating that it is a primary rearrangement in this carcinoma.…”

mentioning

confidence: 99%

Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck

Persson

Andrén

Mark

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

712

639

View full text Add to dashboard Cite

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“…11 Slides were subsequently G-banded and analyzed according to the guidelines of the International System for Human Cytogenetic Nomenclature. 12 FISH analysis was performed on touch preparations prepared from a tumor of generation V as well as on unbanded metaphase chromosomes using whole chromosome painting probes for the human X chromosome and chromosome 1 (wcp X and 1; Vysis, Downers Grove, IL).…”

Section: Cytogenetic and Fluorescence In Situ Hybridization (Fish) Anmentioning

confidence: 99%

A Transplantable Human Carcinoid as Model for Somatostatin Receptor-Mediated and Amine Transporter-Mediated Radionuclide Uptake

Kölby¹,

Bernhardt²,

Ahlman³

et al. 2001

The American Journal of Pathology

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Midgut carcinoid tumors are derived from the enterochromaffin cells in the small intestine. In metastatic disease these tumors can give rise to severe hormonal symptoms because of excessive production of serotonin (5-HT) and tachykinins (substance P and neurokinins). Carcinoid tumors express numerous somatostatin receptors that can be used to alleviate hormonal symptoms by treatment with the long-acting somatostatin analogue octreotide. These receptors have also been used for visualization of tumors by scintigraphy and in receptor-guided surgery and may serve as targets for radionuclide therapy.

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“…There are a handful of salivary gland tumors that have been demonstrated to have recurring cytogenetic abnormalities including adenoid cystic carcinomas [t(6;9) (MYB-NFIB)] [8][9][10], mucoepidermoid carcinomas [t(11:19) (MECT1-MAML2)] [11,12], pleomorphic adenomas (PLAG1 and HMGA2 rearrangements) [13][14][15][16][17], and hyalinizing clear cell carcinoma [t(12;22) (EWSR1-ATF)] [18,19]. In the majority of these tumors, the morphology is distinctive enough to allow for a diagnosis and molecular confirmation is typically not necessary.…”

Section: Introductionmentioning

confidence: 99%

Morphology in Conjunction with Immunohistochemistry is Sufficient for the Diagnosis of Mammary Analogue Secretory Carcinoma

Shah

Wenig

LeGallo

et al. 2014

Head and Neck Pathol

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The recently described mammary analogue secretory carcinoma (MASC) is a low-grade salivary gland malignancy that harbors the recurrent cytogenetic abnormality t(12;15) (p13;q25) ETV6-NTRK3. Confirmation of this is currently considered the gold standard for diagnosis. Some have postulated that morphology together with supporting immunohistochemistry is sufficient to diagnose MASC. In this study we retrospectively review a series of 19 MASCs diagnosed based on histology in conjunction with immunohistochemistry; subsequently we performed in situ hybridization using an ETV6 break-apart probe. Immunohistochemistry for S100 protein and mammaglobin as well as fluorescence in situ hybridization using the Vysis ETV6 Dual Color Break-Apart FISH Probe Kit were performed on all cases. The 19 cases were from 12 females and 7 males with ages ranging from 16 to 76 years (mean = 45 years). Sixteen cases were from the parotid gland, 1 case was from a periparotid lymph node and 2 cases were from the submandibular gland. All 19 cases demonstrated moderate to strong expression of S100 protein. Eighteen cases demonstrated strong, diffuse expression of mammaglobin, while one case had only rare tumor cells that strongly expressed mammaglobin. Eighteen of 19 cases (95 %) demonstrated the ETV6 rearrangement by fluorescence in situ hybridization. Given that morphology together with immunohistochemistry is highly correlated with the ETV6 gene rearrangement, we conclude that molecular confirmation is not required to diagnose MASC.Keywords Mammary analogue secretory carcinoma Á Salivary gland Á ETV6 Á Fluorescence in situ hybridization Á Immunohistochemistry Á Mammaglobin

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Non‐random chromosome rearrangements in adenoid cystic carcinoma of the salivary glands

Cited by 134 publications

References 14 publications

Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck

Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck

A Transplantable Human Carcinoid as Model for Somatostatin Receptor-Mediated and Amine Transporter-Mediated Radionuclide Uptake

Morphology in Conjunction with Immunohistochemistry is Sufficient for the Diagnosis of Mammary Analogue Secretory Carcinoma

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