Detection of RB1 Deletions by Fluorescence In Situ Hybridization in Malignant Hematologic Disorders

Juneau, Amy L.; Kaehler, Marian; Christensen, Eric; Schad, Chris R.; Zinsmeister, Alan R.; Lust, John A.; Hanson, Curtis A.; Dewald, Gordon W.

doi:10.1016/s0165-4608(97)00408-1

Cited by 28 publications

(19 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on their findings, we performed FISH analysis in a group of MM patients with the probes targeting at the similar loci as in Fonseca's study, and we were able to detect chromosomal abnormalities in CD138 ϩ -sorted cells in 72% of the tested MM patients compared with 24% by FISH evaluation performed on unsorted BM cells (P ϭ 0.0016). FISH on CD138 ϩ -sorted cells revealed the frequencies of individual genomic abnormalities in our study population similar to the frequencies observed in prior studies, such as 13q14 deletions in 44% compared with 30 to 54%, 4,6,12,27,28 the p53 deletion in 16.7% compared with 10 to 11%, 12,29 and IgH rearrangements in 44% compared with 50 to 60% in the literature. 30 -32 Of note, FISH on unsorted BM cells identified that the frequencies of individual genomic aberrations in our study series were all lower than those reported in the literature, further supporting FISH on untargeted cells as an inefficient approach for the identification of chromosomal abnormalities in MM.…”

Section: Discussionsupporting

confidence: 88%

A Practical Approach to the Detection of Prognostically Significant Genomic Aberrations in Multiple Myeloma

Chen

Issa

Huang

et al. 2005

The Journal of Molecular Diagnostics

View full text Add to dashboard Cite

Multiple myeloma (MM) is a malignancy of differen-Multiple myeloma (MM) is the prototypic monoclonal Bcell neoplasm that is derived from the autonomous proliferation of plasma cells and associated with paraprotein production and osteolytic bone lesions. MM primarily affects middle-aged to elderly patients. Blacks and males are affected more often than whites and females. 1 MM has remained an incurable disease, and effective therapeutic approaches are urgently required for patients with MM at different risk groups. Standard prognostic factors include serum ␤ 2 -microglobulin, C-reactive protein, bone marrow plasma cell morphology, and plasma cell proliferation (plasma cell labeling index). 1-3 These factors are independently associated with prognosis of patients with MM. Recently, there is considerable interest in characterizing genomic markers to establish prognostic models that allow a better estimation of an individual patient's prognosis.Chromosomal abnormalities are among the most important prognostic parameters for patients with MM. Of particular note, deletions of 13q remain independent adverse prognostic factors. 4 -6 However, conventional karyotyping has been hampered by the slow growth of MM cells in cell cultures, and chromosomal abnormalities are often missed by this technique. Of the cases studied, 50 to 70% showed normal karyotypes originating from the myeloid elements. 7-11 Therefore, cell-targeting methods are essential for the analysis of genomic aberrations in MM.Fluorescent in situ hybridization (FISH) allows detection of chromosomal aberrations in both actively dividing cells and interphase nuclei. Recently, the cytoplasm immunoglobulin (Ig) enhanced interphase FISH has been used to detect the most common genomic abnormalities in 351 patients with MM, including deletions of 13q14 and 17p13.1 and 14q32 translocations [t(4,14)(p16;q32), t(14;16)(q32;q23), and t(11;14)(q13;q32)]. 12 Genomic aberrations have been detected in 54.2% of the tested population for 13q14 deletions, 33.1% for 14q32 translocations, and 10.7% for the 17p13.1 deletion. 12 Importantly, three distinct prognostic groups have been identified, including those with a median survival time of 24.7 months [the t(4;14) and/or t(14;16), and/or 17p13.1 deletion], 42.3 months [13q14 deletions without the t(4;14), t(14;16), or 17p13.1 deletion], and 50.5 months [only the

show abstract

Section: Discussionsupporting

confidence: 88%

A Practical Approach to the Detection of Prognostically Significant Genomic Aberrations in Multiple Myeloma

Chen

Issa

Huang

et al. 2005

The Journal of Molecular Diagnostics

View full text Add to dashboard Cite

show abstract

“…However, another study, using FISH to detect Rb-1 deletions, reported hemizygous gene deletion only in those cases with 13qÀ on standard cytogenetic analysis. 99 Similarly, Tanaka et al 100 reported Rb-1 allelic loss, in addition to the microsatellite loci D13S319 and D13S25, in cases of myeloid malignancy with deletion/translocation at 13q14. Two further studies have confirmed these findings and emphasized that 13q deletions are associated with considerable genetic loss.…”

Section: Chromosome 13mentioning

confidence: 95%

Pathogenetic insight and prognostic information from standard and molecular cytogenetic studies in the BCR-ABL-negative myeloproliferative neoplasms (MPNs)

Reilly

2008

Leukemia

View full text Add to dashboard Cite

The frequency of cytogenetic abnormalities in the Philadelphianegative myeloproliferative neoplasms (MPNs) varies from approximately 30% in primary myelofibrosis (PMF) to less than 5% in essential thrombocytosis (ET). The spectrum of aberrations is heterogeneous, ranging from gains and losses of genetic material to structural changes including unbalanced translocations. However, no specific abnormality has been identified to date. Nevertheless, such investigations can provide evidence of clonality and, as a result, cytogenetic findings have been included in the WHO diagnostic criteria for this group of diseases. The aim of the current review is to discuss the pathogenetic insight and prognostic information that standard, as well as molecular cytogenetic analysis has provided. A brief overview is given of the cytogenetic findings in the individual diseases, followed by a more detailed discussion of the possible pathogenetic consequences of specific abnormalities and their impact on prognosis.

show abstract

“…[10][11][12][13] The only significant discrepancy in prevalence is with the study from the University of Arkansas where they found deletions of chromosome 13 in 86% of patients when using a panel of FISH probes extending over the q-arm. 14 The significance of this observation is unknown and needs to be confirmed by other investigators.…”

Section: Figurementioning

confidence: 99%

“…6,7 Tricot and colleagues have associated the presence of 13q− with an adverse prognosis in patients with MM 8,9 and proposed this genomic abnormality as one of the most important prognostic factors for MM patients. Interphase FISH studies have described a prevalence of the abnormality of 30-50% [10][11][12][13] and also suggest an association with an adverse outcome. 11 Deletions of 13q14 are infrequent in MGUS 13 and are thus believed to be associated with the more advanced stages of disease.…”

Section: Introductionmentioning

confidence: 99%

Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy

Oken²,

et al. 2001

View full text Add to dashboard Cite

Deletions of the long arm of chromosome 13 (13q−) are observed in patients with multiple myeloma (MM), are rarely observed in the monoclonal gammopathy of undetermined significance (MGUS) and have been associated with a worsened prognosis in MM. However, no minimally deleted region in the13q arm has been defined at 13q, and consequently no tumor suppressor genes have yet been identified that are important for disease pathogenesis. We attempted to characterize these chromosome 13q deletions at the molecular cytogenetic level. We studied 351 newly diagnosed patients, entered into the E9486/E9487 clinical study of the Eastern Cooperative Oncology Group. Fluorescent in situ hybridization (FISH) combined with immune fluorescent detection (cIg-FISH) of clonal plasma cells (PC) and cytomorphology were used to analyze interphase, bone marrow (BM) cell, cytospin slides. We simultaneously used DNA probes for the following locus specific probes (LSI); LSI 13 (Rb) and D13S319, which hybridize to 13q14. We subsequently studied distal deletions using the D13S25 probe (13q14.3) and a subtelomeric probe (13qSTP) for the 13q-arm (D13S327) in 40 cases with documented LSI 13 (Rb)/D13S319 deletion and 40 without deletion of these loci. Of 325 evaluable patients, we found 13q deletions in 176 (54%) using LSI 13 (Rb) and D13S319 probes. Of 40 patients with LSI 13 (Rb)/D13S319 deletions, 34 (85%) had coexistent deletion of both D13S25/13qSTP. These results indicate that chromosome 13 deletions in MM involve loss of most if not all of the 13q arm perhaps even indicating monosomy. In six cases the 13qSTP signal was conserved, but D13S25 was lost indicating large interstitial deletions involving 13q14. In 39 of the 40 cases without LSI 13 (Rb)/D13S319 deletions, the normal pattern of two pairs of signals was observed for D13S25/13qSTP. Deletions involving 13q14 are very common in MM as detected by cIg-FISH. These deletions appear to predominantly involve loss of large segments of the 13q arm or monosomy 13, and only occasionally represent an interstitial deletion. Leukemia (2001) 15, 981-986.

show abstract

Detection of RB1 Deletions by Fluorescence In Situ Hybridization in Malignant Hematologic Disorders

Cited by 28 publications

References 13 publications

A Practical Approach to the Detection of Prognostically Significant Genomic Aberrations in Multiple Myeloma

A Practical Approach to the Detection of Prognostically Significant Genomic Aberrations in Multiple Myeloma

Pathogenetic insight and prognostic information from standard and molecular cytogenetic studies in the BCR-ABL-negative myeloproliferative neoplasms (MPNs)

Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy

Contact Info

Product

Resources

About