Vergleich numerischer und struktureller Aberrationen in HPV-positiven und HPV-negativen Kopf-Hals-Tumorzelllinien

Tumors of the head and neck region (HNSCC) are either induced by noxa such as alcohol and tobacco or by a permanent infection with the human papillomavirus (HPV). The second group is considered as a separate entity with preference especially for the oropharynx. Overall incidence of HNSCC is declining, while the incidence of HPV-positive HNSCC appears to increase especially in Europe, Japan and USA. The respective patients are generally younger with less co-morbidities, but more importantly show a much better response to treatment, especially radiochemotherapy. Data from The Cancer Genome Atlas (TCGA) indicate that these two entities appear not to differ with respect to the amount of mutations or copy number variations but differ in gene expression. The aim of the present project was to examine for the first time whether these two entities might differ in DNA content, or numerical and structural chromosomal aberrations. The study was performed with five cell lines of each entity and DNA content was determined by flow cytometry and numerical and structural aberrations using G-banded metaphase chromosomes as well as m-FISH. For both entities there was an enormous variation in both DNA content and number of chromosomes with an excellent correlation between these two parameters. However, on average there was no significant difference between HPV-negative and -positive HNSCC cell lines, neither for DNA content nor for the number of chromosomes. The level of aneuploidy was also determined for each specific chromosome. For both entities, a substantial variation was seen ranging between diploid, triploid as well as tetraploid. Surprisingly, except for chromosome 7 an astonishing similarity was seen for HPV-negative and -positive cell lines. An almost identical pattern was reported for the only two other data sets known so far. This finding suggests that in HNSCC cells this variation is highly regulated and independent of HPV status. For structural chromosomal aberrations for HPV-negative cell lines overall a very heterogeneous pattern was seen, in contrast to HPV-positive cell lines, where a special preference was detected for chromosome 2, 3 and 5. For chromosome 3 the number of translocations was significantly higher for HPV-positive when compared to HPV-negative cell lines. It is suggested that the elevated genomic instability detected for chromosome 3 might lead to the enhanced response of HPV-positive HNSCC found for radiochemotherapy.