Search

Interphase fluorescence in situ hybridization (iFISH) is increasingly used for the identification of BCR/ABL gene rearrangements in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). In the present study, we have explored the incidence of both typical and atypical iFISH patterns of BCR/ABL gene rearrangements in a series of 168 consecutive BCR/ABL+ patients--135 CML, 31 precursor B-ALL and two acute myeloblastic leukemia (AML) cases--and established their underlying genetic alterations through further molecular and chromosome analyses. Two different FISH probes (Vysis Inc., Downers Grove, IL, USA) were used: the LSI BCR/ABL dual color extra signal (ES) and the dual color dual fusion BCR/ABL probe (D-FISH). Our results show that most BCR/ABL+ patients (83%, including 88% of all CML, 61% of ALL and one of two AML) displayed typical iFISH patterns of either Major (M) BCR/ABL (87% of CML, 13% of ALL and one of the two AML) or minor (m) BCR/ABL gene rearrangements (1% of all CML and 48% of ALL cases) with the two probes. Further molecular and cytogenetic studies confirmed the presence of such typical rearrangements in all except one of these ALL cases who had coexistence of an MBCR/ABL and an mBCR/ABL gene rearrangement together with monosomy 9. In the remaining 29 cases (17%), up to five different atypical iFISH patterns were detected with the ES probe. Atypical iFISH patterns were most frequently due to additional numerical changes--most often supernumerary Philadelphia (Ph) chromosome (7%) but also gain or loss of chromosome 9 (1%) or 22 (1%). Deletion of 9q sequences proximal to the breakpoint were also frequently observed with the ES probe (8%). Application of the D-FISH probe showed that in most of these latter cases (5%) deletion of 22q sequences distal to the breakpoint also occurred. The remaining cases with atypical iFISH had cryptic insertion of BCR in 9q34 (1%). Exact interpretation of each iFISH pattern was supported by FISH on metaphases and molecular determination of the BCR breakpoint. In summary, our results indicate that despite the high incidence of typical iFISH patterns of BCR/ABL gene rearrangements, atypical patterns are also found in BCR/ABL+ acute leukemias; the precise definition of the alteration present in individual cases is dependent on metaphase studies and molecular definition of the breakpoint.

Background: Meningiomas usually are considered to be benign tumors; however, 10-20% of cases recur. Few disease characteristics have proved to have prognostic impact for predicting disease free survival. The objective of the current study was to explore the prognostic value of numeric abnormalities of chromosome 22 for meningioma patients., Methods: In this study, the authors prospectively analyzed the incidence of numeric chromosome abnormalities of chromosome 22 by interphase fluorescence in situ hybridization, using a specific probe for the bcr gene located in chromosome 22q11.2, on a total of 88 consecutive meningioma patients. The authors also analyzed its correlation with both the clinicobiologic characteristics at presentation and the patient's outcome., Results: The authors' results show that monosomy 22 was present in 49% of the cases and that this numeric chromosomal abnormality is not associated with other prognostic features of the disease. In contrast, gains (trisomy/tetrasomy) of chromosome 22 were detected in 8 (9%) cases who simultaneously showed gains for other chromosomes and represent an adverse prognostic factor regarding disease free survival (P = 0.001); in addition, trisomy/tetrasomy 22 was more frequently related to younger patients (P = 0.001), aggressive histopathologic features (P < 0.000), a greater incidence of DNA aneuploidy (P =0.006), and a higher proportion of S-phase tumor cells (P = 0.02)., Conclusions: In summary, the authors conclude that loss of a copy of chromosome 22 is a frequent finding in meningioma tumors, but it does not affect the clinical outcome of these patients. In contrast, gains (trisomy/tetrasomy) of chromosome 22, in the context of an hyperdiploid karyotype, although much less frequent, are associated with a more aggressive disease course., (Copyright 2001 American Cancer Society.)