Contact info

Calle Martin Jose Olaya 162, Miraflores.

7058964

990100079

icgeneticsstudies@gmail.com

Abstract

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm composed of monomorphic small to medium-sized atypical lymphocytes arising from naïve mantle zone B-cells, with a generally aggressive and incurable clinical course. The t(11;14)(q13;q32) between IGH@ and CCND1 is present in almost all cases of MCL. Secondary cytogenetic abnormalities are common, and have been associated in some cases with clinical progression. Variant and cryptic t(11;14) translocations have been reported as well. Herein, we present the case of an 80-year old woman with classical MCL, and a cryptic t(11;14) translocation detected by fluorescence in situ hybridization (FISH), and not by conventional cytogenetics. FISH on previously G-banded metaphases showed a cryptic CCND1-IGH@ fusion signal on a derivative chromosome 10, and another fusion signal on one of the abnormal copies of chromosome 11. Cases such as this highlight the importance of FISH studies as part of an algorithmic and multidisciplinary approach to diagnosis.
Key Words: Mantle Cell Lymphoma, cryptic t(11;14), FISH on previously G-banded metaphases
Download the full paper HERE.
Category: Scientific Papers

An unusual complex karyotype in myopericytoma

Saturday, 07 February 2015 00:00

Abstract

Introduction: Myopericytoma is a perivascular neoplasm commonly found in the skin and soft tissue of extremities. These lesions often exhibit concentric vascular proliferation of spindle shaped myoid cells. Methods/Results: We present a case of a 76-year old male who was diagnosed with myopericytoma and subsequent cytogenetic analysis found a highly abnormal karyotype. This karyotype includes cytogenetic mutations that have not been described in previous case studies of myopericytoma. Conclusions: Some of these aberrations occur on genes that are involved in hedgehog signaling as well as pericyte proliferation, indicating a potential pericyte origin for myopericytoma tumors.
Download the full paper HERE.
Category: Scientific Papers

Abstract

The 8p11 myeloproliferative syndrome (EMS) is a rare and aggressive hematological neoplasm caused by rearrangements involving fibroblast growth factor receptor 1 (FGFR1) gene on chromosome 8p11, and one of 11 identified partner genes. The result is a variety of fusion genes encoding aberrant tyrosine kinases and activating multiple signal transduction pathways [1,2].
Involvement of t(8;22)/BCR-FGFR1 is exceedingly rare, with only 8 cases reported to date [3]. It usually presents as chronic myelogenous leukemia (CML)-like disease rapidly evolving into acute myeloid leukemia (AML), but one reported case presented as Bacute lymphoblastic leukemia (B-ALL) [3]. Herein, we report the second case of t(8;22) presenting as B-ALL, and the first to be treated with targeted therapy against tyrosine kinase following chemotherapy. 
Download the full paper HERE.
Category: Scientific Papers

Abstract

Fluorescence in situ hybridization (FISH) analysis of the bone marrow of a 24-year-old man diagnosed with acute promyelocytic leukemia (APL) revealed a variant pattern with one fusion signal instead of the typical two fusions expected with the probe set used. The combined FISH and conventional chromosome analyses suggested that two subsequent translocations had occurred in this patient involving the same chromosomes 15 and 17. As the prognostic outcome in APL is strictly associated with the presence of a PML/RARA fusion, it is useful and necessary to perform both cytogenetic and FISH analyses of a variant t(15;17) to determine the status of the PML/RARA fusion.  2005 Elsevier Inc. All rights reserved.
Download the full paper HERE.
Category: Scientific Papers

Introduction

The t(8;21) translocation occurs in 5e12% of acute myeloid leukemia (AML) cases, often occurring in the younger population. This translocation fuses the RUNX1 gene (previously AML1) on chromosome band 21q22 to the RUNX1T1 (previously known as ETO) on 8q22, resulting in a RUNX1/RUNX1T1 hybrid transcript on the derivative chromosome 8 [1,2]. According to the World Health Organization, this type of AML is associated with a favorable prognosis [1]. Variant translocations account for approximately 3e4% of all AML-M2 with RUNX1/RUNX1T1 fusion transcripts [3], and the clinical consequences of such variants are less clearly defined. Here, we present a case of AML-M2 with a cryptic three-way translocation, t(1;21;8)(p36;q22;q22).

Download the full paper HERE.

Category: Scientific Papers

Abstract

In chronic myelogenous leukemia, chromosomal abnormalities in Philadelphia-negative cells are rare and usually transient, but can infrequently lead to myelodysplastic syndrome and/or acute myeloid leukemia. We report an 82-ear-old patient with an 11-year history of chronic myelogenous leukemia, in complete cytogenetic response, who developed Philadelphia-negative t(15;17)/PMLRARA acute promyelocytic leukemia. This isolated case reaffirms several important clinicopathologic and biologic aspects of chronic myelogenous leukemia, and sheds a unique light on its Philadelphia-negative hematopoiesis. It also underlines the importance of continued cytogenetic monitoring of patients in complete cytogenetic response for the emergence of new chromosomal abnormalities.
Keywords: Chronic myeloid leukemia, chromosomal abnormalities, Philadelphia chromosomenegative, acute promyelocytic leukemia, imatinib
 
Download the full paper HERE.
Category: Scientific Papers

Abstract

Disorders of sex development (DSD) comprise a group of conditions in which genotypes do not correlate with the typical male and female phenotypes. Numerical and structural abnormalities involving both autosomes and sex chromosomes have been observed in DSD. Specifically, deletions, duplications, and translocations involving specific genes as well as point mutations and less common aberrations have been implicated in the pathogenesis of these conditions. Finally, recent advances in analytical tools, namely chromosomal microarrays and sequencing methods, have greatly enhanced the precision with which DSD are genetically characterized and phenotypically correlated. Herein, we review the genes and loci involved in the pathogenesis of disorders of sex development based on recent findings and illustrate the importance of cytogenetics and molecular genetics in the clinical management of these conditions.

Key Words: disorders of sex development (DSD), SRY, cytogenetics, FISH

Download the full paper HERE.

Category: Scientific Papers

Abstract

Chronic myelogenous leukemia (CML) is characterized by the specific cytogenetic translocation t(9;22)(q34;q11.2), also called the Philadelphia (Ph) chromosome. We present a case of a cryptic BCR/ABL1 fusion, which was not originally detected by standard karyotyping. The patient is a forty-seven-year-old man who presented with leukocytosis. Bone marrow biopsy was consistent with CML in chronic phase with no increase in myeloblasts. Conventional cytogenetic studies revealed a 46,XY karyotype. Despite this finding, the patient was started on hydroxyurea therapy followed by Gleevec. At six-month follow-up, a repeat karyotype was again normal, though FISH analysis was positive for BCR/ABL1 fusion. FISH performed on previously G-banded metaphases showed a very rare cryptic insertion involving 22q11. While most genetic abnormalities in CML can be diagnosed using classical cytogenetics, molecular studies remain the gold standard in definitively identifying the characteristic BCR/ALB1 fusion. This case represents one of the variant cryptic rearrangements in CML where clinical correlation with morphologic, immunophenotypic, cytogenetics and FISH findings are indicated and highlights the importance of molecular testing at the time of primary diagnosis.

Download the full paper HERE.

Category: Scientific Papers

Abstract

The t(8;14)(q24.1;q32), the cytogenetic hallmark of Burkitt’s lymphoma, is also found, but rarely, in cases of chronic lymphocytic leukemia (CLL). Such translocation typically results in a MYC-IGH@ fusion subsequently deregulating and overexpressing MYC on der 14q32. In CLL, atypical rearrangements resulting in its gain or loss, within or outside of IGH@ or MYC locus, have been reported, but their clinical significance remains uncertain. Herein, we report a 67 year-old male with complex cytogenetic findings of apparently balanced t(8;14) and unreported complex rearrangements of IGH@ and MYC loci. His clinical, morphological and immunophenotypic features were consistent with the diagnosis of CLL.
Interphase FISH studies revealed deletions of 11q22.3 and 13q14.3, and an extra copy of IGH@, indicative of rearrangement. Karyotype analysis showed an apparently balanced t(8;14)(q24.1;q32). Sequential GPG-metaphase FISH studies revealed abnormal signal patterns: rearrangement of IGH break apart probe with the 5’-IGH@ on derivative 8q24.1 and the 3’-IGH@ retained on der 14q; absence of MYC break apart-specific signal on der 8q; and, the presence of unsplit 5’-MYC-3’ break apart probe signals on der 14q. The breakpoint on 8q24.1 was found to be at least 400 Kb upstream of 5’ of MYC. In addition, FISH studies revealed two abnormal clones; one with 13q14.3 deletion, and the other, with concurrent 11q deletion and atypical rearrangements. Chromosome microarray analysis (CMA) detected a 7.1 Mb deletion on 11q22.3-q23.3 including ATM, a finding consistent with FISH results. While no significant copy number gain or loss observed on chromosomes 8, 12 and 13, a 455 Kb microdeletion of uncertain clinical significance was detected on 14q32.33.
Immunohistochemistry showed co-expression of CD19, CD5, and CD23, positive ZAP-70 expression and absence of MYC expression. Overall findings reveal an apparently balanced t(8;14) and atypical complex rearrangements involving 3’-IGH@ and a breakpoint at least 400 Kb upstream of MYC, resulting in the relocation of the intact 5’-MYC-3’ from der 8q, and apposition to 3’-IGH@ at der 14q. This case report provides unique and additional cytogenetic data that may be of clinical significance in such a rare finding in CLL. It also highlights the utility of conventional and sequential metaphase FISH in understanding complex chromosome anomalies and their association with other clinical findings in patients with CLL. To the best of our knowledge, this is the first CLL reported case with such an atypical rearrangement in a patient with a negative MYC expression.
Keywords: MYC/IGH, FISH, CLL, Microarray
 
Download the full paper HERE.
Category: Scientific Papers

Epigenetics

Thursday, 29 January 2015 00:00

Genomic Imprinting

Genomic imprinting is caused by alterations in chromatin in certain locations of the genome that occur in the germline of one parent, but not of the other parent. These alterations include the covalent modification of DNA, such as methylation of cytosine to form 5-methylcytosine, or the modification or substitution in chromatin of specific histone types, which can influence gene expression within a chromosomal region. The allelic expression of an imprinted gene depends upon whether it resided in the male or female of the previous generation. Imprinted expression can also vary between tissues, developmental stages, and species.

Download the full paper HERE.

Category: Scientific Papers
Page 1 of 2

Visit Chiclayo