7 research outputs found
The role of high-risk human papillomavirus in periocular cancers
Philosophiae Doctor - PhDPurpose: High risk human papillomavirus (HR-HPV) is well established as a causative agent of squamous
cell carcinoma (SCC) of the orophaynx. HR-HPV has also been reported in periocular cancers and
precancers, but controversy exists about its overall incidence and clinicopathologic profile. The purpose of
this study is to evaluate the role of HR-HPV infection in periocular cancers and precancers, using multiple
methods of detection.
Design: Retrospective observational case series with laboratory investigations.
Methods: Sequential surgical samples of 87 carcinomas (invasive SCC, SCC in situ and sebaceous
carcinoma) from three different periocular sites (conjunctiva, lacrimal sac and the eyelid) diagnosed over a
15-year period (2000-2015) were selected for evaluation. Unstained paraffin sections of 87 cases of
periocular carcinomas were analyzed with immunohistochemistry (IHC) for p16 as a screening test.
p16 positive conjunctival- and lacrimal sac SCC were further evaluated for HR-HPV using DNA in situ
hybridization (DNA ISH), and a subset was also analyzed by DNA Polymerase Chain Reaction (DNA
PCR). p16 positive periocular sebaceous carcinomas (SC) were analyzed with PCR, and a subset of 18cases
was further studied with a novel method of mRNA ISH, an advanced technique with an enhanced sensitivity
and specificity. Relevant patient clinical information was obtained from review of the electronic medical
records
Adenomatoid odontogenic tumour in the anterior mandible: a case report
Adenomatoid odontogenic tumours are hamartomatous lesions that rarely deviate from their well-recognised radiological features. However, increasing numbers with atypical radiological features have been reported in recent years. This study reports on a large extrafollicular lesion in the anterior mandible with uncommon radiological features in a 17-year-old female. Treatment included enucleation with a histopathological confirmation. Healing was uneventful
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An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma
Translocation events are frequent in cancer and may create chimeric fusions or âregulatory rearrangementsâ that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps reveal distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers interact with the MYB promoter. Remarkably, MYB protein binds to the translocated enhancers, creating a positive feedback loop that sustains its expression. MYB also binds enhancers that drive different regulatory programs in alternate cell lineages in ACC, cooperating with TP63 in myoepithelial cells and a Notch program in luminal epithelial cells. Bromodomain inhibitors slow tumor growth in ACC primagraft models in vivo. Thus, our study identifies super-enhancer translocations that drive MYB expression and provides insight into downstream MYB functions in the alternate ACC lineages