3D Telomeric Fingerprint of Advanced Cutaneous T-Cell Lymphoma: A Pilot Study
Oncogenic events of cutaneous T-cell lymphomas (CTCLs) progression remain elusive. Telomere remodeling, a manifestation of genetic instability, is associated with progression of some malignancies. We aim to characterize the three-dimensional (3D) telomeric organization in CTCLs. We performed 3D telomeric quantitative FISH (3D Telo-q-FISH) of skin tissue of 9 patients with CTCL and control lymphocytes. Reported parameters included telomeres of low intensity (TLI), number and intensity of telomeric signals, telomere aggregates and nuclear volume. Stratification was based on CD30 expression and clinical stage. CTCLs had more TLIs than controls (27% vs 16%, p<0.0001). TLI proportion was higher in CD30-high cells than CD30-low cells (34% vs 22%, p<0.0001) and in the advanced group compared to the early group (30% vs 24%, p<0.0001). CD30 expression and advanced stage were associated with larger nuclei and more telomeres and advanced stage cells had significantly more aggregates. We show that 3D Telo-QFISH is feasible in small skin biopsies with limited tissue, and we report evidence that advanced CTCLs are associated with an increased proportion of TLIs, a hallmark feature in many tumor cells. Our analysis suggests that CTCL cells undergo in a first step telomere shortening and loss compared to healthy controls. In a second step further telomeric shortening associated with chromosomal rearrangements and Breakage-fusion-Bridge cycles may be involved in the progression of CTCL.