Thyroid-Like Cholangiocarcinoma: Histopathological, Immunohistochemical, In-Situ Hybridization and Molecular Studies on an Uncommon Emerging Entity

2021 ◽  
pp. 106689692110139
Author(s):  
Erika Hissong ◽  
Kenrry Chiu ◽  
Hyeon Park ◽  
James Solomon ◽  
Wei Song ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chromatin Remodeling ◽  
Thyroid Tumor ◽  
Cytokeratin 7 ◽  
Histologic Subtype ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Peripheral Type ◽  
Detailed Molecular Analysis

Thyroid-like cholangiocarcinoma is a very uncommon variant of peripheral-type cholangiocarcinoma. To date, only 4 prior cases have been reported. The molecular features of this tumor have not been described. We report a case of a 60-year-old woman with a tumor that evolved over a period of 10 years. A left hepatectomy specimen showed an 11 cm tumor that on histology exhibited areas reminiscent of a thyroid tumor with follicular and insular features which were positive on immunohistochemistry for cytokeratin 7 and in-situ hybridization for albumin. A detailed molecular analysis failed to show mutations common to cholangiocarcinomas but revealed frameshift mutations in 2 chromatin-remodeling genes, CREBBP and KMNT2A. This case confirms that thyroid-like cholangiocarcinoma is a histologic variant of this tumor that is associated with relatively low growth. As most cholangiocarcinomas, it is diffusely positive for cytokeratin 7 and albumin by in-situ hybridization. Given its rarity, the molecular alterations in this specific histologic subtype remain to be fully elucidated.

scholarly journals Molecular specializations of deep cortical layer analogs in songbirds

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander A. Nevue ◽  
Peter V. Lovell ◽  
Morgan Wirthlin ◽  
Claudio V. Mello
Keyword(s):  
In Situ Hybridization ◽  
Motor Function ◽  
Vocal Learning ◽  
Cortical Layer ◽  
Cortical Layers ◽  
Behavioral Traits ◽  
Molecular Features ◽  
Brain Circuitry ◽  
Learning Circuits

Abstract How the evolution of complex behavioral traits is associated with the emergence of novel brain pathways is largely unknown. Songbirds, like humans, learn vocalizations via tutor imitation and possess a specialized brain circuitry to support this behavior. In a comprehensive in situ hybridization effort, we show that the zebra finch vocal robust nucleus of the arcopallium (RA) shares numerous markers (e.g. SNCA, PVALB) with the adjacent dorsal intermediate arcopallium (AId), an avian analog of mammalian deep cortical layers with involvement in motor function. We also identify markers truly unique to RA and thus likely linked to modulation of vocal motor function (e.g. KCNC1, GABRE), including a subset of the known shared markers between RA and human laryngeal motor cortex (e.g. SLIT1, RTN4R, LINGO1, PLXNC1). The data provide novel insights into molecular features unique to vocal learning circuits, and lend support for the motor theory for vocal learning origin.

scholarly journals Exome Sequencing Implicates SWI/SNF Chromatin Remodeling Genes in Human Congenital Hydrocephalus

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
August A Allocco ◽  
Sheng Chih Jin ◽  
Weilai Dong ◽  
Xue Zeng ◽  
Sierra B Conine ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Brain Development ◽  
Candidate Genes ◽  
Chromatin Remodeling ◽  
Congenital Hydrocephalus ◽  
Normal Brain ◽  
Csf Flow ◽  
Neurodevelopmental Outcomes ◽  
Xenopus Embryos

Abstract INTRODUCTION Congenital Hydrocephalus (CH) affects 1 in 1000 live births and is treated with lifelong surgical cerebrospinal fluid (CSF) diversion with substantial morbidity. Our group recently sequenced 180 probands with CH and identified 4 novel CH genes, all of which regulate neural stem cell (NSC) fate. Nonetheless, these genes account for just 10% of studied cases. METHODS We doubled the size of our cohort through robust recruitment and exome-sequenced 361 CH probands, including 216 case-parent trios. To study the effect of novel mutations on brain development, we developed a Xenopus tropicalis model of CH using CRISPR/Cas9. Multiple, nonoverlapping CRISPR guide RNAs targeted against candidate genes were designed and injected into fertilized single cell Xenopus embryos via microinjection. Ventricular morphology and CSF flow dynamics were analyzed via optical coherence tomography (OCT) imaging. Histological sections from WT and mutant Xenopus embryos were subjected to whole-mount in Situ hybridization to assess expression of various markers of NSC growth and proliferation. RESULTS We identified new causative mutations in both previously identified and novel genes, all of which regulate ventricular zone NSC fate. Of these, enrichment in rare, damaging variants was highest in the SWI/SNF chromatin remodeling complex genes SMARCC1 and ARID1B (P = 1.83 × 10-9). Xenopus tadpoles harboring mutations in SMARCC1 exhibited marked ventriculomegaly, aqueductal stenosis, and impaired CSF flow. In Situ hybridization of SMARCC1 knockout brain sections demonstrated decreased expression of genes regulating NSC growth and proliferation. Notably, injection of wild type SMARCC1 RNA restored normal brain development in SMARCC1 KO embryos. CONCLUSION These findings implicate SWI/SNF complex genes in CH and validate the use of Xenopus for investigating additional candidate genes. These findings highlight the importance of NSC dysregulation in CH pathology, and suggest that in a subset of patients the risk of adverse neurodevelopmental outcomes may be unaltered whether or not shunting is performed.

scholarly journals New Developments in Salivary Gland Pathology: Clinically Useful Ancillary Testing and New Potentially Targetable Molecular Alterations

2017 ◽  
Vol 141 (3) ◽  
pp. 381-395 ◽  
Author(s):  
Christopher C. Griffith ◽  
Alessandra C. Schmitt ◽  
James L. Little ◽  
Kelly R. Magliocca
Keyword(s):  
Salivary Gland ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Salivary Gland Tumor ◽  
Molecular Techniques ◽  
Salivary Gland Tumors ◽  
Gland Tumor ◽  
Molecular Alterations ◽  
Tumor Pathology

Accurate diagnosis of salivary gland tumors can be challenging because of the many diagnostic entities, the sometimes extensive morphologic overlap, and the rarity of most tumor types. Ancillary testing is beginning to ameliorate some of these challenges through access to newer immunohistochemical stains and fluorescence in situ hybridization probes, which can limit differential diagnostic considerations in some cases. These ancillary testing strategies are especially useful in small biopsy samples, including aspiration cytology. Molecular techniques are also expanding our understanding of salivary gland tumor pathology and are helping to identify potential targets that may improve treatment for some of these tumors. Here, we summarize the clinical use of new immunohistochemical markers in our practice and review the current understanding of chromosomal rearrangements in salivary gland tumor pathology, emphasizing the prospects for exploiting molecular alterations in salivary gland tumors for diagnosis and targeted therapy. We find that immunohistochemistry and fluorescence in situ hybridization are powerful tools toward the diagnosis of salivary gland tumors, especially when used in a systematic manner based on morphologic differential-diagnostic considerations. As new targeted therapies emerge, it will become increasingly vital to incorporate appropriate molecular testing into the pathologic evaluation of salivary gland cancers.

scholarly journals Pediatric Oligodendrogliomas: A Study of Molecular Alterations on 1p and 19q Using Fluorescence In Situ Hybridization

2003 ◽  
Vol 62 (5) ◽  
pp. 530-537 ◽  
Author(s):  
Ravi Raghavan ◽  
Jyoti Balani ◽  
Arie Perry ◽  
Linda Margraf ◽  
Mary B. Vono ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Molecular Alterations

DNA sequence mapping in interphase and metaphase chromosomes by fluorescence in situ hybridization

1992 ◽  
Vol 50 (1) ◽  
pp. 496-497
Author(s):  
Barbara Trask ◽  
Susan Allen ◽  
Anne Bergmann ◽  
Mari Christensen ◽  
Anne Fertitta ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Dna Sequence ◽  
Dna Sequences ◽  
Dual Band ◽  
Nick Translation ◽  
Metaphase Chromosomes ◽  
Band Pass ◽  
Texas Red ◽  
Fluorescent Spot

Using fluorescence in situ hybridization (FISH), the positions of DNA sequences can be discretely marked with a fluorescent spot. The efficiency of marking DNA sequences of the size cloned in cosmids is 90-95%, and the fluorescent spots produced after FISH are ≈0.3 μm in diameter. Sites of two sequences can be distinguished using two-color FISH. Different reporter molecules, such as biotin or digoxigenin, are incorporated into DNA sequence probes by nick translation. These reporter molecules are labeled after hybridization with different fluorochromes, e.g., FITC and Texas Red. The development of dual band pass filters (Chromatechnology) allows these fluorochromes to be photographed simultaneously without registration shift.

Ultrastructural analysis of the spatial distribution of MRNA

1992 ◽  
Vol 50 (1) ◽  
pp. 552-553
Author(s):  
Gary Bassell ◽  
Robert H. Singer
Keyword(s):  
Electron Microscopy ◽  
Spatial Distribution ◽  
In Situ Hybridization ◽  
High Resolution ◽  
Nucleic Acids ◽  
Colloidal Gold ◽  
Dna Probe ◽  
Nucleotide Analogs ◽  
Gold Particles

We have been investigating the spatial distribution of nucleic acids intracellularly using in situ hybridization. The use of non-isotopic nucleotide analogs incorporated into the DNA probe allows the detection of the probe at its site of hybridization within the cell. This approach therefore is compatible with the high resolution available by electron microscopy. Biotinated or digoxigenated probe can be detected by antibodies conjugated to colloidal gold. Because mRNA serves as a template for the probe fragments, the colloidal gold particles are detected as arrays which allow it to be unequivocally distinguished from background.

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