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FISH identifies inv(16)(p13q22) masked by translocations in three cases of acute myeloid leukemia
J Dierlamm1, M Stul, H Vranckx
1Center for Human Genetics, University of Leuven, Belgium.
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: 1) 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.
Insights
The inversion 16 (inv(16)) in acute myeloid leukemia (AML) can be masked by other chromosomal abnormalities. Fluorescence in situ hybridization (FISH) and molecular analyses reliably detect masked inv(16) in AML.
Area of Science:
- Hematology and Oncology
- Cytogenetics
- Molecular Biology
Background:
- Acute myeloid leukemia (AML) is a heterogeneous group of hematologic malignancies.
- The inversion 16 chromosome abnormality, inv(16)(p13q22), is a recurrent genetic alteration associated with AML.
- Variant translocations involving chromosome 16 can complicate the diagnosis of inv(16).
Observation:
- Three adult AML patients (M2 and M4Eo subtypes) presented with chromosomal abnormalities initially obscuring inv(16).
- Cytogenetic analysis revealed complex rearrangements including translocations and deletions involving chromosome 16.
- Fluorescence in situ hybridization (FISH) and molecular analyses (RT-PCR, Southern blot) were employed to investigate these cases.
Findings:
- FISH successfully identified inv(16) in all three cases, often masked by other structural changes like translocations (t(9;16), t(1;16)) and deletions (del(16)).
- Molecular analysis confirmed the presence of a CBFB-MYH11 fusion transcript and MYH11 rearrangement in all patients.
- A small interstitial deletion at 16p13 proximal to the MYH11 breakpoint was noted in one case.
Implications:
- inv(16) can be concealed by other chromosomal abnormalities, necessitating advanced diagnostic techniques.
- Variant translocations previously uncharacterized at the molecular level may represent masked inv(16) rearrangements.
- FISH, RT-PCR, and Southern blot are crucial for accurate detection of masked inv(16) in AML cases with chromosome 16 structural changes.