Rapid detection of chromosome 16 inversion in acute nonlymphocytic leukemia, subtype M4: regional localization of the breakpoint in 16p

Abstract

The pericentric inversion of chromosome 16 characteristic for acute nonlymphocytic leukemia, subtype M4, was detected in five patients by means of nonradioactive in situ hybridization of complete cosmids. First, five cosmids situated along the short arm of chromosome 16 were used to map the breakpoint of the inversion distal to the rare folate-sensitive fragile site FRA16A. Then, the use of two cosmids on either side of the breakpoint, combined with a probe specific for the centromeric region of chromosome 16, readily detected the inversion, even in poor metaphase spreads.

Analysis of genes and chromosomes by nonisotopic in situ hybridization

“…In certain diagnostic applications, such as the detection of trisomy 21, small probes are more informative than painting of whole chromosomes, because the more focal signals are easier to quantitate [48,160]. Furthermore, Single probes flanking or spanning a chromosomal breakpoint can be used to detect a diagnostically important breaking event [161][162][163] or to characterize further a breakpoint region [11,164,165]. An example of a breakpoint in the short arm of chromosome 11 from a Potter's facies Syndrome patient was previously reported and is shown in Figure IB.…”

Translocation (8;21) in acute nonlymphocytic leukemia delineated by chromosomal in situ suppression hybridization

“…Painting of whole chromosomes using DNA libraries from sorted chromosomes provides the advantage that translocations involving any material from the painted chromosome can be detected. CISS hybridization of appropriate cosmid or YAC clones may be used for the identification of still smaller translocations, deletions, or inversions, as well as for the precise definition of breakpoints [11][12][13][14][15][16][17][18][19].…”

Use of dual-color interphase FISH for the detection of inv(16) in acute myeloid leukemia at diagnosis, relapse and during follow-up: a study of 23 patients

“…3,4 Several studies have suggested that the presence of inv (16) is an important prognostic indicator in AML patients, as it is associated with a relatively favorable outcome: 90% of patients obtain CR, with nearly 50% being disease-free survivors at 5 years. 5,6 The inv (16) may be difficult to be detected with CC, particularly when poor quality metaphases are obtained from leuCorrespondence: M Mancini, Department of Cellular Biotechnologies and Hematology, University 'La Sapienza', Via Benevento 6, 00161 Rome, Italy; Fax: 0039-06-85795537 Received 3 January 1998; accepted 18 October 1999 kemic cells. Moreover, CC cannot detect cryptic deletions of sequences centromeric to the p-arm breakpoint which have been described in a subset of inv(16) AML patients, accounting for 18-33% of cases.…”

“…FISH probes, previously reported to detect inv (16) are the cosmids C36 and C40, suitable only for metaphases 15 and a yeast artificial chromosome (YAC) probe, spanning the 16p breakpoint. 16 Although applicable on interphase cells, the YAC gives false negative results in cases of concomitant 16p deletion.…”

“…16 Although applicable on interphase cells, the YAC gives false negative results in cases of concomitant 16p deletion. 16 In the present study we analyzed 23 AML patients with CC clear or suspected inv (16), using a new set of cosmid contigs that allows interphase analysis, 8 with the aim of evaluating the efficacy of interphase dual-color FISH in detecting inv (16) at the onset of the disease, through its course and at relapse. Results were compared with CC and RT-PCR analysis of CBF␤/MYH11 transcript.…”