BAP1 ‐inactivated melanocytic tumors demonstrate prominent centrosome amplification and associated loss of primary cilia

2021 ◽  
Author(s):  
Julia Ye ◽  
Kathleen M. Sheahon ◽  
Philip E LeBoit ◽  
Timothy H. McCalmont ◽  
Ursula E. Lang
Keyword(s):  
Primary Cilia ◽  
Centrosome Amplification ◽  
Melanocytic Tumors

scholarly journals Over-expression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse

Open Biology ◽  
2015 ◽  
Vol 5 (12) ◽  
pp. 150209 ◽  
Author(s):  
Paula A. Coelho ◽  
Leah Bury ◽  
Marta N. Shahbazi ◽  
Kifayathullah Liakath-Ali ◽  
Peri H. Tate ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Primary Cultures ◽  
Centrosome Amplification ◽  
Proliferating Cells ◽  
Differentiation Markers ◽  
Over Expression ◽  
Centriole Duplication ◽  
Keratin 5 ◽  
Tumour Formation ◽  
Tumour Suppressor P53

To address the long-known relationship between supernumerary centrosomes and cancer, we have generated a transgenic mouse that permits inducible expression of the master regulator of centriole duplication, Polo-like-kinase-4 (Plk4). Over-expression of Plk4 from this transgene advances the onset of tumour formation that occurs in the absence of the tumour suppressor p53. Plk4 over-expression also leads to hyperproliferation of cells in the pancreas and skin that is enhanced in a p53 null background. Pancreatic islets become enlarged following Plk4 over-expression as a result of equal expansion of α- and β-cells, which exhibit centrosome amplification. Mice overexpressing Plk4 develop grey hair due to a loss of differentiated melanocytes and bald patches of skin associated with a thickening of the epidermis. This reflects an increase in proliferating cells expressing keratin 5 in the basal epidermal layer and the expansion of these cells into suprabasal layers. Such cells also express keratin 6, a marker for hyperplasia. This is paralleled by a decreased expression of later differentiation markers, involucrin, filaggrin and loricrin. Proliferating cells showed an increase in centrosome number and a loss of primary cilia, events that were mirrored in primary cultures of keratinocytes established from these animals. We discuss how repeated duplication of centrioles appears to prevent the formation of basal bodies leading to loss of primary cilia, disruption of signalling and thereby aberrant differentiation of cells within the epidermis. The absence of p53 permits cells with increased centrosomes to continue dividing, thus setting up a neoplastic state of error prone mitoses, a prerequisite for cancer development.

scholarly journals Truncation of POC1A associated with short stature and extreme insulin resistance

2015 ◽  
Vol 55 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Jian-Hua Chen ◽  
Maria Segni ◽  
Felicity Payne ◽  
Isabel Huang-Doran ◽  
Alison Sleigh ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Primary Cilia ◽  
Centrosome Amplification ◽  
Facial Dysmorphism ◽  
Mitotic Spindles ◽  
Multipolar Spindle ◽  
Molecular Defects ◽  
Primordial Dwarfism ◽  
Extreme Insulin Resistance

We describe a female proband with primordial dwarfism, skeletal dysplasia, facial dysmorphism, extreme dyslipidaemic insulin resistance and fatty liver associated with a novel homozygous frameshift mutation in POC1A, predicted to affect two of the three protein products of the gene. POC1A encodes a protein associated with centrioles throughout the cell cycle and implicated in both mitotic spindle and primary ciliary function. Three homozygous mutations affecting all isoforms of POC1A have recently been implicated in a similar syndrome of primordial dwarfism, although no detailed metabolic phenotypes were described. Primary cells from the proband we describe exhibited increased centrosome amplification and multipolar spindle formation during mitosis, but showed normal DNA content, arguing against mitotic skipping, cleavage failure or cell fusion. Despite evidence of increased DNA damage in cells with supernumerary centrosomes, no aneuploidy was detected. Extensive centrosome clustering both at mitotic spindles and in primary cilia mitigated the consequences of centrosome amplification, and primary ciliary formation was normal. Although further metabolic studies of patients with POC1A mutations are warranted, we suggest that POC1A may be added to ALMS1 and PCNT as examples of centrosomal or pericentriolar proteins whose dysfunction leads to extreme dyslipidaemic insulin resistance. Further investigation of links between these molecular defects and adipose tissue dysfunction is likely to yield insights into mechanisms of adipose tissue maintenance and regeneration that are critical to metabolic health.

Large Vulvar Lipoma in an Adolescent: A Case Report

JMS SKIMS ◽  
2011 ◽  
Vol 14 (1) ◽  
pp. 28-29
Author(s):  
R K Maurya ◽  
Pawan Kumar Singh ◽  
Sandeep Singh
Keyword(s):  
Case Report ◽  
Epithelial Cell ◽  
Adolescent Girl ◽  
Rare Case ◽  
Mesenchymal Cell ◽  
Benign Tumors ◽  
Melanocytic Tumors

Lipomas of vulva have been reported only rarely. Benign tumors of the vulva are normally classified according to their origin as epithelial cell tumors (e.g., keratinocytic, adnexal and ectopic tumors), or mesenchymal cell tumors (e.g., vascular, fibrous, muscular, neural, adipose and melanocytic tumors). Vulvar lipomas need to be differentiated from liposarcomas, which are rare but are very similar to lipomas clinically. Here we present a rare case of large vulvar lipoma in an adolescent girl. JMS 2011;14(1):28-29

Primary Melanocytoma of the Lower Thoracic Spinal Cord: Case report and review of the literature

2019 ◽  
Vol 8 (1) ◽  
pp. 5
Author(s):  
Dimitrios Panagopoulos
Keyword(s):  
Total Resection ◽  
Thoracic Spinal Cord ◽  
Meningeal Melanocytoma ◽  
Melanocytic Tumors ◽  
Thoracic Spinal ◽  
Thoracolumbar Region ◽  
Rare Benign Tumor ◽  
Mri Scans ◽  
History Of ◽  
The Central Nervous System

Background: Meningeal melanocytoma is a rare benign tumor, most frequently located in the posterior fossa and spinal canal. Our objective is to illustrate a case of this tumor that originated in the thoracolumbar area of the spine and had an uneventful clinical course after total resection. Case description: We present the case of a 59 years old woman who presented with a medical history of ongoing neurological deterioration due to spastic paresis of the lower extremities. MRI of the thoracolumbar region identified a melanocytic melanoma as the underlying cause. Conclusions: Melanocytic tumors of the central nervous system have a typical appearance on MRI scans, varying with the content and distribution of melanin. However, the differential diagnosis between malignant melanoma and melanocytoma still depends on pathological criteria. Spinal meningeal melanocytoma has a benign course, and it is amenable for gross total resection. The outcome is favorable following complete resection.

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