FISH Probes

INTRODUCTION:The human CBFB genes encode a protein named Core-binding factor subunit beta.
The protein encoded by this gene is the beta subunit of a heterodimeric core-binding transcription factor belonging to the PEBP2/CBF transcription factor family which master-regulates a host of genes specific to hematopoiesis (e.g., RUNX1) and osteogenesis (e.g., RUNX2).Rearrangements and abnormal expression of the CBFB gene – also known as CBFb or PEBP2B – have been observed in acute myeloid leukemia (AML) and other hematological malignancies.
INTENDED USE: The CBFB Break Apart FISH probe Kit t is designed to detect rearrangements in the human CBFB gene located on chromosome band 16q22.1. In addition to revealing breaks, which can lead to translocation of parts of the gene, inversion, or its fusion to other genes, the probe set can also be used to identify other CBFB aberrations such as deletions or amplifications.

PROBE DESCRIPTION:The 5’ centromeric fragment of the CBFB Break Apart FISH Probe kit labeled with the fluorochrome CytoOrange covers the 5’ (start) portion of the CBFB gene and some adjacent genomic sequences. The 3’ Telomeric fragment of the CBFB Break apart FISH Probe Kit labeled with CytoGreen covers the 3’ (end) part as well as sequences downstream of the gene. The two probes are flanking sequences across the CBFB gene in which variable breakpoints have been observed.

INTRODUCTION: CDKN2A, also known as cyclin-dependent kinase Inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. It is ubiquitously expressed in many tissues and cell types. The gene codes for two proteins, including the INK4 family members, p16 (or p16INK4a) and p14arf. Both act as tumor suppressors by regulating the cell cycle. Abnormalities in CDKN2A – also known as ARF, MLM, P14, P16, P19, CMM2, INK4, MTS1, TP16, CDK4I, CDKN2, INK4A, MTS-1, P14ARF, P19ARF, P16INK4, P16INK4A or P16-INK4A – occur in gliomas and meningioma’s as well as numerous other familial and sporadic tumor types.
INTENDED USE: The CDKN2A/CCP9 FISH Probe Kit is designed to detect the human CDKN2A gene located on chromosome band 9p21.3, along with the number of chromosome 9 copies per cell and measure the copy number of the human CDKN2A gene located on chromosome band 9p21.3.

PROBE DESCRIPTION: The CDKN2A Probe of the CDKN2A/CCP9 FISH Probe kit labeled with the fluorochrome CytoOrange covers a chromosomal region which includes the entire CDKN2A gene. The CCP9 Probe of the CDKN2A/CCP9 FISH Probe kit labeled with the flourochrome CytoGreen is derived from chromosome 9-specific alpha satellite DNA is designed to serve as a control to determine the number of chromosome 9 copies per cell.

INTRODUCTION:The CSF1R gene (known also as c-FMS) is a receptor for a cytokine called colony stimulating factor 1 that in humans encode cell-surface protein called Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115 (Cluster of Differentiation 115). he encoded protein is a single pass type I membrane protein and acts as the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. The EGR1 gene encode in humans a protein called EGR-1 (Early growth response protein 1) also known as Zif268 (zinc finger protein 225) or NGFI-A (nerve growth factor-induced protein A). EGR-1 is a transcription factor. Abnormalities in CSF1R – also known as FMS, CSFR, FIM2, HDLS, CFMS, CD115, CSF1R or M-CSF-R – and abnormalities in EGR1 – also Known as ERBB, HER1, mENA, ERBB1, PIG61 or NISBD2 – have been observed in myeloid malignancies, lung cancer and several other cancer types.
INTENDED USE: The CSF1R/EGR1 FISH Probe Kit is designed to detect the human CSF1R gene, located on chromosome band 5q32, and the EGR1 gene on chromosome band 5q31.2.

PROBE DESCRIPTION:The CSF1R Probe of the CSF1R/EGR1 FISH Probe kit labeled with the fluorochrome CytoOrange covers a chromosomal region which includes the entire CSF1R gene. The EGR1 Probe of the CSF1R/EGR1 FISH Probe Kit labeled with CytoGreen covers a chromosomal region which includes the entire EGR1 gene. Both probes are designed to measure the copy number of the human CSF1R and EGR1 gene located on chromosome band 5q32 and 5q31.2, respectively.

INTRODUCTION:The DLEU1 gene was originally identified as a potential tumor suppressor gene.The ZBTB16 gene is a member of the Kruppel C2H2 type zinc finger protein family and encodes a transcription factor containing nine Kruppel-type zinc finger domains at the C-terminus. The ZBTB16 protein is located in the cell nucleus and is involved in the progression of the cell cycle, interacting with histone deacetylases. Rearrangements and abnormal expression of the DLEU1 gene region – also known as BCMS, DLB1, LEU1, LEU2, XTP6, BCMS1, DLEU2, LINC00021 or NCRNA00021 – have been observed in B-cell chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and other malignancies. Fusions and aberrant expression of the ZBTB16 gene – also known as PLZF or ZNF145 – have been reported in acute promyelocytic leukemia and other neoplasias.
INTENDED USE: The DLEU1/ZBTB16 FISH Probe Kit is designed to detect the human DLEU1 gene, located on chromosome band 13q14.2, and the ZBTB16 gene on chromosome band 11q23.2.

PROBE DESCRIPTION:The DLEU1 Probe of the DLEU1/ZBTB16 FISH Probe kit labeled with the fluorochrome CytoOrange covers a chromosomal region which includes the majority of the DLEU1 gene and genomic sequences adjacent to the 5′ end of the gene. The ZBTB16 Probe of the DLEU1/ZBTB16 FISH Probe Kit labeled with CytoGreen e covers a chromosomal region which includes the entire ZBTB16 gene. Both probes are designed to measure the copy number of the human DLEU1 and ZBTB16 genes located on chromosome bands 13q14.2 and 11q23.2, respectively.

INTRODUCTION: Members of the BCL2 family of proteins play important roles in the control of programmed cell death (apoptosis). They comprise proteins that facilitate apoptosis, as well as apoptosis inhibitors. Lymphomas are malignant conditions of the lymphatic part of the circulatory system. One of the most frequent subtypes of lymphoma in adults is follicular lymphoma, a cancer originating in certain B cells that is often symptomless in its early stages. Nearly half of lymphomas diagnosed in adults are of the follicular subtype. One of the widely recognized molecular characteristics of this subtype of the condition is that BCL2 is regularly dysregulated in follicular lymphomas, most often by gene translocation. In fact, BCL2 protein has been detected in virtually all transformed cells in samples from follicular lymphoma patients, whereas it was not seen in non-neoplastic cells or in normal lymph nodes. One particularly common rearrangement is a reciprocal translocation, in which the BCL2 gene, normally on chromosome 18, is relocated to the immunoglobulin heavy chain (IGH) gene region on chromosome 14 and is overexpressed under the influence of an enhancer element on that locus. However, fusion of BCL2 with other genes, including AFF3 and the IGHL@ and IGK@ gene loci, has also been observed.

INTENDED USE: The IGH-BCL2 Fusion/Translocation FISH probe kit is designed to detect rearrangements involving regions of the human IGH locus, located on chromosome band 14q32.33, and of the human BCL2 gene on 18q21.33. The kit contains two differentially labeled Locus Specific Probe (LSP) pairs. One set of probes covers the 5’ (start) portion of the BCL2 gene and some upstream untranslated genomic sequence as well as sequences downstream of the 3’ (end) part of the gene. The two probes are flanking sequences on both sides and inside the BCL2 gene where breakpoint clusters and individual breakpoints have been found. The second probe pair spans the immunoglobulin heavy chain gene locus (IGH@) and consists of a portion matching the 5’ (start) region encoding variable gene segments (IGHV), and a part that covers the 3’ (end) and downstream sequences. This probe pair is flanking an area of the IGH gene comprising constant gene segments (IGHC) as well as the delta segment (IGHD), joining region (IGHJ) and epsilon domain (IGHE). Almost all known breakpoints in IGH@have been mapped to this region.

PROBE DESCRIPTION: The BCL2 Probe of the IGH-BCL2 Fusion/Translocation FISH Probe Kit labeled with the fluorochrome CytoOrange covers some genomic sequences adjacent to the 5’ (start) portion of the BCL2 gene; it also covers sequences downstream of the 3’ end of the gene. The IGH Probe of the IGH-BCL2 Fusion/Translocation FISH Probe Kit labeled with the fluorochrome CytoGreen covers the 5’ and the center sequences of the IGH locus, and it also covers the 3’ (end) part and the neighboring downstream region.

INTRODUCTION: Cyclin D1, also called B-cell leukemia/lymphoma 1 (BCL1) or parathyroid adenomatosis 1 (PRAD1), belongs to a family of highly conserved proteins that serve as key regulators of the cell cycle. They form complexes with, and thereby regulate the activity of cyclin-dependent kinases (CDKs), a family of protein kinase enzymes required for progression through the cell cycle. Cyclin D1 is overexpressed in many tumor types. For example, it has been found amplified, and proven to be a marker of poor prognosis, in a percentage of breast cancer cases. CCND1 is also aberrantly activated in a number of hematological malignancies. It is mainly found in mantle cell lymphoma (MCL), a relatively rare non-Hodgkin’s lymphoma type. The most common translocation in MCL is one in which CCND1 is moved to the IGH locus on chromosome 14; juxtaposition of the two genes leads to activation of the CCND1 gene via enhancer elements in the IGH locus. However, fusion of CCND1 with other genes, including FSTL3 and the IGHL@ and IGK@ gene loci, has also been observed. CCND1 activation by translocation also occurs in B-prolymphocytic leukemia, plasma cell leukemia, splenic lymphoma with villous lymphocytes and sometimes in chronic lymphocytic leukemia and multiple myeloma. Detection of CCND1 gene translocation is now widely recommended for the discernment of specific lymphoma subtypes. Furthermore, it is a predictor of improved survival in multiple myeloma patients.
INTENDED USE: The IGH-CCND1 Fusion/Translocation FISH probe kit is designed to detect rearrangements involving regions of the human IGH locus, located on chromosome band 14q32.33, and of the human CCND1 gene on 11q13.3. The kit contains two differentially labeled Locus Specific Probe (LSP) pairs. One set of probes covers the 5’ (start) portion of the CCND1 gene and some upstream untranslated genomic sequence as well as sequences downstream of the 3’ (end) part of the gene. The two probes are flanking sequences in the CCND1gene in which both a 3’ breakpoint cluster as well as several individual breakpoints have been observed.

PROBE DESCRIPTION: The IGH Probe of the IGH-CCND1 Fusion/Translocation FISH Probe Kit labeled with the fluorochrome CytoGreen covers the 5’ and the center sequences of the IGH locus, and it also covers the 3’ (end) part and the neighboring downstream region. The CCND1 Probe of the IGH-CCND1 Fusion/Translocation FISH Probe Kit labeled with the fluorochrome CytoOrange covers some genomic sequences adjacent to the 5’ (start) portion of the CCND1 gene; it also covers sequences downstream of the 3’ end of the gene. The probe set is optimized to reveal translocations between the two regions.

INTRODUCTION: Rearrangements and abnormal expression of the MYC gene (also known as MRTL, MYCC, c-Myc or bHLHe39) have been described in Burkitt’s lymphoma, where its positivity has diagnostic utility within a clinical, morphological and immunohistochemical context. On the other hand, in large or non-classifiable diffuse B-cell lymphoma, the MYC translocation has a prognostic value and dictates a more aggressive treatment of the neoplasm. On the other hand, together with the determination of the translocation of the BCL2 and BCL6 genes, it aims to establish the double or triple-hit character of the neoplasm. Other hematological neoplasms, myelomas, as well as breast, cervical, colon, ovarian and other tumors may present MYC translocation.
Most Burkitt lymphoma cases show the t(8;14)(q24;q32) [MYC-IGH] and less commonly the t(8;22)(q24;q11) or t(2;8)(p12;q24). The translocation is present in both the endemic African Burkitt lymphoma and in the non-endemic tumor type (Europe, America, and Japan). In case the Burkitt lymphoma infiltrated the bone marrow (leukemic phase) the MYC-translocation can be demonstrated in the bone marrow or blood as well.
INTENDED USE: The IGH-MYC Fusion/Translocation FISH probe kit t is designed to detect rearrangements involving the human IGH locus and MYC gene, located on chromosome bands 14q32.33 and 8q24.21, respectively.

PROBE DESCRIPTION: The IGH Probe of the IGH-MYC Fusion/Translocation FISH Probe Kit labeled with the fluorochrome CytoGreen covers the 5’ and the center sequences of the IGH locus, and it also covers the 3’ (end) part and the neighboring downstream region. The MYC Probe of the IGH-MYC Fusion/Translocation FISH Probe Kit labeled with the fluorochrome CytoOrange covers some genomic sequences downstream of the 5’ (start) portion of the MYC gene, and it also covers the sequences adjacent to the 3’ end of the gene. The probe set is optimized to reveal translocations between the two regions.

INTRODUCTION: The MYEOV gene was originally isolated by the application of the NIH/3T3 tumorigenicity assay with DNA from a gastric carcinoma. The chromosomal region 11q13 is frequently associated with genetic rearrangements in a large number of human malignancies, including B-cell malignancies and overexpression of MYEOV is frequently observed in breast tumors and oral, esophageal squamous cell carcinomas and multiple myeloma. MYEOV is a putative oncogene, located 360kb away from CCND1, which is thought to be activated in the translocation by becoming closely associated with IGH enhancers. The mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with an aggressive clinical course. It is genetically characterized by t(11;14)(q13;q32) and is present in about 95% of MCL patients. By lower frequency, t(11;14) is also detectable in B-cell prolymphocytic leukemia, myelomas and chronic lymphocytic leukemia. In multiple myeloma (MM), t(11;14) is the most common translocation, detectable in about 15-20% of all MM patients by FISH.
INTENDED USE: The IGH-MYEOV Fusion/Translocation FISH probe kit is designed to detect rearrangements involving the human IGH locus and MYEOV gene located on chromosome bands 14q32.33 and 11q13.3, respectively.

PROBE DESCRIPTION:The IGH Probe of the IGH-MYEOV Fusion/Translocation FISH Probe Kit labeled with the fluorochrome CytoGreen covers the 5’ and the center sequences of the IGH locus; it also covers the 3’ part and the neighboring downstream region. The MYEOV Probe of the IGH-MYEOV Fusion/Translocation FISH Probe Kit labeled with the fluorochrome CytoOrange covers a chromosomal region which includes the entire MYEOV gene. The probe set is optimized to reveal translocations between the two regions.

INTRODUCTION: Rearrangements and abnormal expression of the IRF4 gene – also known as NF-EM5, MUM1, LSIRF or IRF-4 – and the DUSP22 gene – also called JKAP, JSP-1, JSP1, LMW-DSP2, LMWDSP2, MKP-x, MKPX or VHX – have been observed in multiple myeloma (MM) and other lymphoid malignancies, viral malignancies, skin cancer and lymphomatoid papulosis (LyP), a chronic papulonecrotic or papulonodular skin disease with histologic features suggestive of a malignant lymphoma.
INTENDED USE: The IRF4/DUSP22 Break Apart FISH probe Kit is designed to detect rearrangements in the human IRF4 and DUSP22 genes and the surrounding regions located on chromosome band 6p25.3. In addition to revealing breaks, which can lead to translocation of parts of the genes, inversion, or their fusion to other genes, the probe set can also be used to identify other IRF4 and DUSP22 aberrations such as deletions or amplifications.

PROBE DESCRIPTION:The 5’ telomeric fragment of the IRF4/DUSP22 Break Apart FISH Probe kit labeled with the fluorochrome CytoGreen covers the entire DUSP22 gene, genomic sequences adjacent to the 5’ (start) and the 3′ (end) portions of the gene, and genomic sequences upstream of the IRF4 gene’s 5′ (start) end. The 3’ centromeric fragment of the IRF4/DUSP22 Break apart FISH Probe Kit labeled with CytoOrange covers some sequences downstream of the 3’ end of the IRF4 gene. The two probes are flanking sequences across the IRF4 and DUSP22 genes in which various breakpoints have been observed.