TET2 haplo-insufficiency occurs through different molecular mechanisms and is 
promptly revealed by array comparative genomic hybridization, single nucleotide 
polymorphism (SNP) array, and next-generation sequencing (NGS). Fluorescence in 
situ hybridization (FISH) can effectively demonstrate TET2 deletions and is 
often used to validate molecular results. In the present study 41 MDS patients 
with and without 4q abnormalities were analyzed with a series of bacterial 
artificial chromosome (BAC) probes spanning the 4q22.3-q25 region. On 
conventional cytogenetic (CC) studies, a structural defect of the long arm of 
chromosome 4 (4q) was observed in seven patients. In three, one each with a 
t(1;4)(p21;q24), an ins(5;4)(q23;q24qter), and a t(4;17)(q31;p13) as the sole 
chromosomal abnormality, FISH with the RP11-356L5 and RP11-16G16 probes, which 
cover the TET2 locus, produced one signal only. Unexpectedly, this same result 
was achieved in 3 of the remaining 34 patients. Thus, a TET2 deletion was 
observed in a total of six patients (14.6%). TET2 deletion was not correlated 
with any particular clinical findings or outcome. These findings demonstrate 
that 1) FISH is an effective and economical method to reveal cryptic 
abnormalities of band 4q22-q24 resulting in TET2 deletions; 2) in these 
patients, TET2 deletion is the unifying genetic event; and 3) the different 
breakpoints within the 4q22-q25 region suggest that deletions are not mediated 
by repetitive sequences.