scholarly journals Clonality Assessment in a Case of Multifocal Adamantinoma and a Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Paul Borbas ◽  
Andreas Leithner ◽  
Patrick Sadoghi ◽  
Anne Berndt ◽  
Bernadette Liegl ◽  
...  
Keyword(s):  
Trinucleotide Repeat ◽  
De Novo ◽  
Receptor Gene ◽  
Bone Tumour ◽  
X Inactivation ◽  
Cag Repeat ◽  
Fmr1 Gene ◽  
Low Grade ◽  
Regional Metastases ◽  
Inactivation Pattern

Adamantinoma is a low-grade, malignant biphasic bone tumour predominantly located in the tibia. In up to 50% of all cases this is combined with one or more lesions in the ipsilateral fibula. Whether these lesions represent regional metastases or arise de novo is not yet exactly known. In order to address this question, we extracted DNA from the respective fresh frozen tumour tissues in a case of a young woman with a multifocal adamantinoma of both the tibia and ipsilateral fibula. Afterwards the X inactivation pattern was studied by means of methylation-sensitive polymerase chain reaction and primers that target the polymorphic CGG trinucleotide repeat of FMR1 gene and the polymorphic CAG repeat, on exon 1 of the human androgen receptor gene (AR). The analysis of the AR was homozygous and not informative. Studying the FMR1 gene, we detected a 100% skewing of the X inactivation pattern of both locations and found that the same allele was methylated. Even if the fibula lesion arose de novo there would have been a 50 : 50 chance that the same allele was methylated. As this methylation pattern was found we cannot provide a valid explanation for the origin of the fibula lesion. Analysis of X inactivation patterns in future cases of polyfocal adamantinoma might provide further evidence for one of the two theories.

Clonality of Isolated Eosinophils in the Hypereosinophilic Syndrome

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1651-1657 ◽  
Author(s):  
Hsiao-Wen Chang ◽  
Kah-Hoo Leong ◽  
Dow-Rhoon Koh ◽  
Szu-Hee Lee
Keyword(s):  
Trinucleotide Repeat ◽  
Receptor Gene ◽  
Hypereosinophilic Syndrome ◽  
Parasitic Infection ◽  
Androgen Receptor Gene ◽  
Multiple Organ ◽  
X Inactivation ◽  
Low Grade ◽  
Specific Test ◽  
Blood Eosinophils

Abstract The idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by unexplained, persistent eosinophilia associated with multiple organ dysfunction due to eosinophilic tissue infiltration. In the absence of karyotypic abnormalities, there is no specific test to detect clonal eosinophilia in IHES. Analysis of X-chromosome inactivation patterns can be used to determine whether proliferative disorders are clonal in origin. Methylation of HpaII andHha I sites near the polymorphic trinucleotide repeat of the human androgen receptor gene (HUMARA) has been shown to correlate with X-inactivation. In this study, we have used the polymerase chain reaction (PCR) with nested primers to analyze X-inactivation patterns of the HUMARA loci in purified eosinophils from female patients with eosinophilia. Peripheral blood eosinophils were isolated by their autofluoresence using flow cytometric sorting. Eosinophils purified from a female patient presenting with IHES were found to show a clonal pattern of X-inactivation. Eosinophil-depleted leukocytes from this patient were polyclonal by HUMARA analysis, thus excluding skewedness of random X-inactivation. After corticosteroid suppression of her blood eosinophilia, a clonal population of eosinophils could no longer be detected in purified eosinophils. In contrast, eosinophils purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy, parasitic infection, or drug reaction showed a polyclonal pattern of X-inactivation by HUMARA analysis. The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have, in reality, a low-grade clonal disorder that can be distinguished from reactive eosinophilias by HUMARA analysis. Further, the method described can be used to monitor disease progression.

Clonality of Isolated Eosinophils in the Hypereosinophilic Syndrome

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1651-1657 ◽  
Author(s):  
Hsiao-Wen Chang ◽  
Kah-Hoo Leong ◽  
Dow-Rhoon Koh ◽  
Szu-Hee Lee
Keyword(s):  
Trinucleotide Repeat ◽  
Receptor Gene ◽  
Hypereosinophilic Syndrome ◽  
Parasitic Infection ◽  
Androgen Receptor Gene ◽  
Multiple Organ ◽  
X Inactivation ◽  
Low Grade ◽  
Specific Test ◽  
Blood Eosinophils

The idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by unexplained, persistent eosinophilia associated with multiple organ dysfunction due to eosinophilic tissue infiltration. In the absence of karyotypic abnormalities, there is no specific test to detect clonal eosinophilia in IHES. Analysis of X-chromosome inactivation patterns can be used to determine whether proliferative disorders are clonal in origin. Methylation of HpaII andHha I sites near the polymorphic trinucleotide repeat of the human androgen receptor gene (HUMARA) has been shown to correlate with X-inactivation. In this study, we have used the polymerase chain reaction (PCR) with nested primers to analyze X-inactivation patterns of the HUMARA loci in purified eosinophils from female patients with eosinophilia. Peripheral blood eosinophils were isolated by their autofluoresence using flow cytometric sorting. Eosinophils purified from a female patient presenting with IHES were found to show a clonal pattern of X-inactivation. Eosinophil-depleted leukocytes from this patient were polyclonal by HUMARA analysis, thus excluding skewedness of random X-inactivation. After corticosteroid suppression of her blood eosinophilia, a clonal population of eosinophils could no longer be detected in purified eosinophils. In contrast, eosinophils purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy, parasitic infection, or drug reaction showed a polyclonal pattern of X-inactivation by HUMARA analysis. The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have, in reality, a low-grade clonal disorder that can be distinguished from reactive eosinophilias by HUMARA analysis. Further, the method described can be used to monitor disease progression.

scholarly journals Androgen Receptor Gene CAG Trinucleotide Repeats in Anovulatory Infertility and Polycystic Ovaries

2000 ◽  
Vol 85 (9) ◽  
pp. 3484-3488 ◽  
Author(s):  
Amparo Mifsud ◽  
Sylvia Ramirez ◽  
E. L. Yong
Keyword(s):  
Androgen Receptor ◽  
Trinucleotide Repeat ◽  
Age Of Onset ◽  
Receptor Gene ◽  
Normal Serum ◽  
Cag Repeat ◽  
Polycystic Ovaries ◽  
Repeat Tract ◽  
Serum Androgens ◽  
Anovulatory Infertility

Abstract Hyperandrogenism is currently thought to be central to the pathogenesis of polycystic ovarian syndrome (PCOS), a common endocrine disorder in premenopausal women characterized by irregular menstruation and anovulatory infertility. Although hyperandrogenism is characteristic, some women with PCOS have normal serum androgen levels. All androgens act through the X-linked androgen receptor (AR), the N-terminal domain of which contains a polyglutamine tract encoded by a highly polymorphic CAG trinucleotide repeat tract. Recently, variations in this CAG microsatellite tract, while remaining within the normal polymorphic range (11–38 CAGs), have been inversely correlated with receptor activity. Thus, short tracts are associated with high intrinsic AR activity and increased severity and earlier age of onset of the androgen-regulated tumor prostate cancer, whereas longer CAG tracts are associated with low AR activity and oligospermic infertility. To investigate the role of the CAG repeat tract in PCOS, we measured its length in 91 patients with ultrasound diagnosis of polycystic ovaries, irregular menstrual cycles, and anovulatory infertility and compared them to 112 control subjects of proven fertility with regular menses. Fluorescent-labeled DNA fragments containing the CAG repeat tract were amplified from leucocytic DNA, and their lengths were compared with internal size markers on an automated DNA Sequencer. There were no differences in the mean CAG length between patients and controls when both alleles were considered together or separately. Because there is a subset of PCOS patients whose serum androgens are normal, we compared differences in CAG length between patients whose serum testosterone (T) levels were below the normal laboratory mean, to those that were higher. There was a trend for a lower mean CAG biallelic length among anovulatory patients with T less than 1.73 nmol/L compared with those whose T was more than 1.73 nmol/L (22.47 ± 0.36 vs. 23.25 ± 0.29). This difference in CAG length between patients with low and high T levels (20.38 ± 0.51 vs. 21.98 ± 0.29) was highly significant (P = 0.004) when only the shorter allele of each individual was considered. Ethnic differences were also evident in our data; Indian subjects had a significantly shorter AR-CAG length compared with Chinese, being 22.08 ± 0.50 and 23.16 ± 0.17, respectively. Our data indicate an association between short CAG repeat length and the subset of anovulatory patients with low serum androgens, suggesting that the pathogenic mechanism of polycystic ovaries in these patients could be due to the increased intrinsic androgenic activity associated with short AR alleles.

De novo interstitial direct duplication of Xq21.1q25 associated with skewed X-inactivation pattern

2004 ◽  
Vol 131A (3) ◽  
pp. 273-280 ◽  
Author(s):  
G. Tachdjian ◽  
A. Aboura ◽  
M. Benkhalifa ◽  
I. Creveaux ◽  
L. Foix-Hélias ◽  
...  
Keyword(s):  
De Novo ◽  
X Inactivation ◽  
Inactivation Pattern ◽  
Skewed X Inactivation

The CAG Repeat Within the Androgen Receptor Gene and Benign Prostatic Hyperplasia

1999 ◽  
Vol 162 (1) ◽  
pp. 269-270
Author(s):  
E. Giovannucci ◽  
E.A. Platz ◽  
M.J. Stampfer ◽  
A. Chan ◽  
K. Krithivas ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Prostatic Hyperplasia ◽  
Cag Repeat

scholarly journals Occurrence of a Clonal T-Cell Population in a Case of Chronic Myelomonocytic Leukemia

2021 ◽  
Vol 14 ◽  
pp. 263485352199150
Author(s):  
Anupama Patil ◽  
Balasaheb Wanve ◽  
Pradeep Kar ◽  
Shanthi Velusamy
Keyword(s):  
T Cell ◽  
Cell Population ◽  
De Novo ◽  
Treatment Guidelines ◽  
Myeloproliferative Neoplasm ◽  
Genetic Mutation ◽  
Pcr Analysis ◽  
Low Grade ◽  
Monocytic Leukemia ◽  
Laboratory Findings

Chronic myelo-monocytic leukemia (CMML) is an aggressive myeloid neoplasm with some features of a myelodysplastic syndrome (MDS) and others of a myeloproliferative neoplasm (MPN). Rarely, patients with CMML have a co-existing lympho-proliferative disorder (LPD). In most cases, the lymphoid neoplasm is diagnosed first, and the CMML is considered to be a secondary therapy-induced form of leukemia. We report herein a unique case of de-novo CMML, with an underlying clonal T-cell population and describe its clinical presentation and laboratory findings. A 70-year old male presented with a 3-month history of cough, dsypnea, abdominal distension, and low-grade fever. Physical and radiological examination revealed hepatosplenomegaly but no lymphadenopathy. Peripheral blood had absolute monocytosis with marrow showing CMML with 10% blasts along with dysplasia in myeloid and erythroid lineages. Flow cytometry indicated possibility of chronic myelo-monocytic leukemia with 13% monocytic cells along with an additional clonal population of gamma/delta T cells (15%) with aberrant immunophenotype. Polymerase chain reaction (PCR) analysis was positive for clonal T-cell rearrangement. A diagnosis of CMML with an underlying clonal T-CLPD was made. The synchronous occurrence of CMML and T-cell neoplasm may be attributed to a genetic mutation common to both. Currently, there are no treatment guidelines for group of patients; hence individualized therapeutic strategies should be implemented to enable symptomatic improvement and provide optimum care.

Association Between Androgen Receptor Gene CAG Repeat Polymorphism and Plasma Testosterone Levels in Postmenopausal Women

2005 ◽  
Vol 12 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Ilma Simoni Brum ◽  
Poli Mara Spritzer ◽  
Franyoise Paris ◽  
Maria Augusta Maturana ◽  
Franyoise Audran ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Postmenopausal Women ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Cag Repeat ◽  
Plasma Testosterone ◽  
Repeat Polymorphism ◽  
Testosterone Levels

The GGN and CAG repeat polymorphisms in the exon-1 of the androgen receptor gene are, respectively, associated with insulin resistance in men and with dyslipidemia in women

2009 ◽  
Vol 113 (3-5) ◽  
pp. 202-208 ◽  
Author(s):  
Germán Rodríguez-González ◽  
Raquel Ramírez-Moreno ◽  
Patricia Pérez ◽  
Cristina Bilbao ◽  
Laura López-Ríos ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Androgen Receptor ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Cag Repeat ◽  
Exon 1

scholarly journals De-novo multilayering in fibrovascular pigment epithelial detachment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manoj Soman ◽  
Jay U. Sheth ◽  
Asmita Indurkar ◽  
Padmanabhan Meleth ◽  
Unnikrishnan Nair
Keyword(s):  
De Novo ◽  
Median Number ◽  
Final Visit ◽  
Low Grade ◽  
Vascular Endothelial ◽  
Pigment Epithelial Detachment ◽  
Pigment Epithelial ◽  
Anti Vegf ◽  
Significant Difference ◽  
Endothelial Growth Factor

AbstractThis study describes the occurrence of multilayered pigment-epithelial detachment (MLPED) as a De-novo phenomenon (DN-MLPED) and compare the features with multi-layering secondary to chronic anti-vascular endothelial growth factor (anti-VEGF) therapy (s-MLPED). We did a retrospective evaluation of spectral-domain optical coherence tomography (SD-OCT) features, treatment-profile, and visual-acuity (VA) outcomes in eyes with MLPED. Out of 17 eyes with MLPED, 7 eyes had DN-MLPED and 10 eyes had s-MLPED. There was no significant difference in baseline and final VA between the groups. At the final visit, no significant visual improvement was noted in both the groups, although a possible trend towards an improvement was seen in DN-MLPED eyes while the s-MLPED demonstrated a declining trend (DN-MLPED—LogMAR-BCVA: Baseline = 0.79 [∼ 20/123] ± 0.91; Final = 0.76 [∼ 20/115] ± 0.73; p = 0.87; s-MLPED—LogMAR BCVA: Baseline = 0.43 [∼ 20/54] ± 0.68; Final = 0.94 [∼ 20/174] ± 0.71; p = 0.06). Moreover, after presentation, the median number of injections in DN-MLPED eyes were significantly lower compared to s-MLPED eyes (DN-MLPED:4; s-MLPED:12; p = 0.03) (Median follow-up: DN-MLPED = 26 months; s-MLPED = 54 months; p = 0.15). Subretinal hyperreflective-material (SHRM) deposition heralded the onset of multilayering and was seen to progress in all DN-PED eyes and 1/4 eyes of s-MLPED. To conclude, MLPED is a unique form of cicatrizing fibrovascular-PED which can evolve denovo too. Long-standing disease with intermittent or low-grade activity can potentially explain this unique phenomenon. With fewer anti-VEGF therapy, the de-novo MLPED eyes show more visual stability as compared to s-MLPED eyes.

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