The Principles of Clinical Cytogenetics - Extra Materials - Springer

Fluorescence In Situ Hybridization 469
Table 5
FISH for Hematologic Malignancies
Chromosomal Chromosome– Disease
Aberration a gene(s) involved association b Probe type(s) c
t (9;22)(q34;
q11.2) 9—ABL1 CML, ALL, AML DCDF, DCSF,
22—BCR DCES, FCDF
t(15;17)(q22;q21.1) 15—PML AML DCDF, DCSF,
17—RARA– BAP
t(*;11)(*.*; q23) 11—MLL ALL, AML BAP
t(8;21)(q22;q22) 8—CBFA2T1(ETO) AML DCDF
21—RUNX1(AML1)
inv(16)(p13q22) or 16q22—CBFβ AML BAP
t(16;16)(p13;q22)
t(12;21)(p13;q22) 12—ETVG(TEL) ALL DCES
21—RUNX1(AML1)
Trisomy 8 8—8cen AML, CML SC
t(8;14)(q24;q32) 8—MYC ALL, NHL DCDF
14—IGH
t(11;14)(q13;q34) 11—CCND1 NHL, MM DCDF
14—IGH
t(14;18)(q32;q21) 14—IGH NHL DCDF
18—BCL2
t(*;14)(*.*;q32) 14—IGH NHL, MM BAP
Del(13)(q14) or –13 Unknown tumor CLL, MM SC, PP
suppressor
Trisomy 12 12—12cen CLL SC, PP
unknown gene(s)
del(11)(q23) ATM CLL SC, PP
del(17)(p13.1) TP53 CLL, MM, NHL SC, PP
a An asterisk (*) is used to delineate multiple loci or breakpoints.
b Abbreviations: ALL = acute lymphoid leukemia; AML = acute myeloid leukemia; CLL = chronic lymphocytic
leukemia; CML = chronic myelogenous leukemia; NHL = non-Hodgkin’s lymphoma; MM = multiple myeloma
c Abbreviations: BAP = break-apart probe; DCDF = dual-color, dual-fusion; DCES = dual-color, extra signal; DCSF
= dual-color, single-fusion; FCDF = four-color, dual-fusion; PP = Probe panel; SC = single color (see Fig. 8).
Chronic Myelogenous Leukemia
The t(9;22)(q34;q11.2) fuses the 5' region of the BCR (breakpoint cluster region) gene at 22q11.2
to the 3' region of the Abelson (ABL1) oncogene at 9q34, producing a novel protein with tyrosine
kinase activity. Multiple commercial FISH probe combinations are available to detect the BCR/ABL1
fusion in situ, including a dual-color, single-fusion (DCSF) probe set that detects BCR/ABL1 on the
“Philadelphia chromosome” [der(22)] (see Fig. 9), a dual-color, single-fusion with an extra signal
(DCES) probe set that detects the der(22) BCR/ABL1 fusion and a residual signal on the der(9) (see
Fig. 9), a dual-color, dual-fusion probe set that detects the fusion products on both derivative chromosomes
(see Figs. 9 and 10) and a four-color, dual-signal exchange probe set (F-FISH) that detects
the translocation products on both derivative chromosomes and allows for identification of the derivatives
in interphase cells (see Fig. 11) (46). Each probe set is useful for identifying the BCR/ABL1
fusion event in diagnostic samples. However, the ES and both the two-color, dual-fusion and fourcolor,
dual-signal exchange probe sets offer increased sensitivity for posttreatment residual disease
detection because the abnormal signal patterns produced by the latter probes rarely occur by random
chance. These are particularly useful for detection of the nearly 20% of patients with a t(9;22)(q34;q11.2)