FISH identifies inv(16)(p13q22) masked by translocations in three cases of acute myeloid leukemia

Abstract

The inv(16)(p13q22) masked by different translocations was detected by fluorescence in situ hybridization (FISH) and confirmed by molecular analysis in three adult patients presenting with acute myeloid leukemia (AML)‐M2 (cases 1 and 3) and M4Eo (case 2). Cytogenetic analysis revealed 47,XX,t(9;16)(p23;p13),+22 (case 1); 46,XX,t(1;16)(p32;p13) (case 2); and 46,XY,?del(16)(q22) (case 3). Using a panel of probes for chromosomes 1, 9, 16, and 20 as well as probes to detect inv(16), i.e., two cosmid contigs hybridizing proximally and distally to the 16p13 breakpoint, FISH demonstrated inv(16) involving the derivative 16 as well as reciprocal translocations between 16q22‐qter and 9p24 (case 1), 1p32 (case 2), and 20q13 (case 3). In addition, a small interstitial del(16)(p13p13) proximal to the MYH11 breakpoint was detected in case 1. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Southern blot analysis showed a CBFB‐MYH11 fusion transcript and MYH11 rearrangement, respectively, in all three cases. We conclude that: l) inv(16) can be masked by other structural abnormalities involving chromosome 16; 2) some of the so‐called variant translocations not explored at the molecular level may in fact represent a masked inv(16); and 3) FISH, RT‐PCR, and Southern blot analyses are reliable tools to detect masked inv(16) and should be applied in all AML cases with structural changes of chromosome 16. Genes Chromosomes Cancer 22:87–94, 1998. © 1998 Wiley‐Liss, Inc.

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

“…20 These probes could also demonstrate the rearrangement in rare cases not detected by RT-PCR because of an unusual breakpoint. 11 More importantly, uncertain cytogenetic results caused by absent or poor quality metaphases will be clarified, beyond doubt.…”

“…15 Furthermore, the proximal probe lies outside and thus does not detect the associated 16p deletion. 20 A YAC covering the breakpoint region and split by inv16 is also available and has been tested in some of the cases studied (data not shown). The YAC gives two spots on normal nuclei and three spots in cells with inv (16).…”

Fluorescence In Situ Hybridization Identifies Cryptic t(16;16)(p13;q22) Masked By del(16)(q22) in a Case of AML-M4 Eo

“…6 -8,12,13 Several studies report the retrospective identification of a "masked" or missed inv(16)/t(16;16) in leukemias with positive RT-PCR results. 5,[13][14][15][16][17] While these studies suggest a higher detection sensitivity of RT-PCR for identifying the CBF␤-MYH11, there exists the possibility of falsepositive RT-PCR results. 5,9 Indeed, there are instances where false-positive PCR results have been reconciled as negative on repeat evaluation after finding no evidence for inv(16)/t(16;16) by cytogenetics or FISH analysis.…”

Screening for core binding factor gene rearrangements in acute myeloid leukemia

“…Therefore, in cases of AML lacking the classic t(8;21) one should be alerted to the possibility of a cryptic AML1-ETO rearrangement on detection of del(9q) and/or loss of a sex chromosome, 10,22,32 or of a cryptic CBF␤-MYH11 fusion in the presence of +22, 13,14,16,33,34 particularly in conjunction with suggestive morphology. However, it should be appreciated that although cases with cryptic AML1-ETO gene fusions may share the distinctive morphological features associated with the t(8;21) and those with cryptic CBF␤-MYH11 fusions may exhibit an M4eo phenotype, this is not invariably the case 10,11,13,14,16,23,33,35,36 suggesting that molecular screening should not be solely targeted to such patients. Furthermore, the majority of cases of AML with del(9q) or +22 have been shown not to have underlying cryptic CBF gene rearrangements.…”

“…8 Over the last few years it has become apparent that a proportion of AML cases have an underlying AML1-ETO or CBF␤-MYH11 fusion gene in the apparent absence of the classic t(8;21) or inv(16)/t(16;16), respectively. [9][10][11][12][13][14][15][16] There are a number of potential reasons for this, which may be classified into the following subgroups: …”