Double-target fluorescence in situ hybridization distinguishes multiple genetically aberrant clones in head and neck squamous cell carcinoma.
Genomic heterogeneity has been observed in several solid tumor types. To investigate this phenomenon in head and neck squamous cell carcinoma (HNSCC), we analyzed macroscopically distinct tissue samples of 12 resected tumors by a combination of fluorescence in situ hybridization (FISH) and DNA flow cytometry. Using a panel of centromeric DNA probes, numerical chromosomal aberrations were detected in 10 tumors, 9 of which showed a single DNA aneuploid peak. Imbalances in chromosomal copy numbers resulted in unique patterns of chromosomal aberrations for each tumor case. Two types of tumors could be distinguished, i.e., tumors (n = 5) containing a single aneusomic clone and tumors (n = 5) with multiple aneusomic clones. The center of this latter group of tumors was shown to be genetically more heterogeneous than the tumor margin. In conclusion, this study showed that 1) the pattern of chromosomal aberrations varies greatly between different HNSCC, 2) a major clone with a specific pattern of chromosomal aberrations has spread throughout most HNSCC, and 3) a subgroup of HNSCCs contains additional clones with a different pattern of chromosomal aberrations. Based on these results, HNSCC can be divided into a genetically more homogeneous and a genetically more heterogeneous group.
Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Maastricht and University of Maastricht, The Netherlands. j.veltman@molcelb.unimaas.nl
J A
JA
Veltman
A H
AH
Hopman
S A
SA
van der Vlies
F J
FJ
Bot
F C
FC
Ramaekers
J J
JJ
Manni
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics*; D002999:Clone Cells / Q000145:classification / Q000473:pathology; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D018740:Genetic Heterogeneity; D006258:Head and Neck Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged
D015342:DNA Probes; D004273:DNA, Neoplasm