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Establishment and genetic characterization of six unique tumor cell lines as preclinical models for sinonasal squamous cell carcinoma.

García-Inclán C, López-Hernández A, Alonso-Guervós M, Allonca E, Potes S, Melón S, López F, Llorente JL, Hermsen M - Sci Rep (2014)

Bottom Line: Overexpression of p53 was observed in five, and of EGFR in four cell lines.None of the cell lines showed strong immunopositivity of p16 or presence of human papilloma virus.In conclusion, we have created six new cell lines that are clinically and genetically representative of sinonasal SCC and that will be a useful tool for the preclinical testing of new therapeutic agents.

View Article: PubMed Central - PubMed

Affiliation: Dept. Otolaryngology, IUOPA, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.

ABSTRACT
Sinonasal squamous cell carcinomas (SCC) are rare tumors, etiologically related to occupational exposure to wood and leather dust. In spite of surgical and radiotherapeutic advances, the 5 year survival is still 30-50%. Therefore, alternative treatment options are needed. We report the establishment and characterization of six unique human sinonasal SCC cell lines, named SCCNC1, 2, 4, 5, 6 and 7. In vitro growth and invasion characteristics were evaluated and genetic profiles were compared to those of the original primary tumors. The population doubling times ranged from 21 to 34 hours. Cell lines SCCNC2 and 7 were highly invasive in matrigel. Five cell lines carried a high number of copy number alterations, including amplifications and homozygous deletions, while one showed only three abnormalities. Sequence analysis revealed three cell lines with TP53 mutation and none with KRAS or BRAF. Overexpression of p53 was observed in five, and of EGFR in four cell lines. None of the cell lines showed strong immunopositivity of p16 or presence of human papilloma virus. In conclusion, we have created six new cell lines that are clinically and genetically representative of sinonasal SCC and that will be a useful tool for the preclinical testing of new therapeutic agents.

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Microarray CGH profiles of cell lines at passages between 6 and 10 (left column) and their corresponding primary tumors (right column).All data points are expressed as log2-ratios, ordered continuously from left to right as chromosome 1 up to chromosome X (here numbered as 23). In cell lines SCCNC1,2,4,6 and 7 many chromosomes show copy number alteration, including homozygous deletion and high level amplification. The majority of the aberrations are also present in the primary tumor. Cell line SCCNC5 harboured only three copy number changes and these were not detected in the primary tumor.
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f3: Microarray CGH profiles of cell lines at passages between 6 and 10 (left column) and their corresponding primary tumors (right column).All data points are expressed as log2-ratios, ordered continuously from left to right as chromosome 1 up to chromosome X (here numbered as 23). In cell lines SCCNC1,2,4,6 and 7 many chromosomes show copy number alteration, including homozygous deletion and high level amplification. The majority of the aberrations are also present in the primary tumor. Cell line SCCNC5 harboured only three copy number changes and these were not detected in the primary tumor.

Mentions: Short tandem repeat fingerprinting performed on DNA from the cell lines and blood lymphocytes from the patients confirmed the individual identity of all cell lines. All cell lines showed at least 90% identical short tandem repeats. Moreover, microarray CGH analysis of DNA extracted from frozen tumor tissue of the primary tumor from which the cell lines were derived, showed an identical pattern of copy number alterations (Figure 3), although the amplitude of the observed gains and losses was higher in the cell lines.


Establishment and genetic characterization of six unique tumor cell lines as preclinical models for sinonasal squamous cell carcinoma.

García-Inclán C, López-Hernández A, Alonso-Guervós M, Allonca E, Potes S, Melón S, López F, Llorente JL, Hermsen M - Sci Rep (2014)

Microarray CGH profiles of cell lines at passages between 6 and 10 (left column) and their corresponding primary tumors (right column).All data points are expressed as log2-ratios, ordered continuously from left to right as chromosome 1 up to chromosome X (here numbered as 23). In cell lines SCCNC1,2,4,6 and 7 many chromosomes show copy number alteration, including homozygous deletion and high level amplification. The majority of the aberrations are also present in the primary tumor. Cell line SCCNC5 harboured only three copy number changes and these were not detected in the primary tumor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017217&req=5

f3: Microarray CGH profiles of cell lines at passages between 6 and 10 (left column) and their corresponding primary tumors (right column).All data points are expressed as log2-ratios, ordered continuously from left to right as chromosome 1 up to chromosome X (here numbered as 23). In cell lines SCCNC1,2,4,6 and 7 many chromosomes show copy number alteration, including homozygous deletion and high level amplification. The majority of the aberrations are also present in the primary tumor. Cell line SCCNC5 harboured only three copy number changes and these were not detected in the primary tumor.
Mentions: Short tandem repeat fingerprinting performed on DNA from the cell lines and blood lymphocytes from the patients confirmed the individual identity of all cell lines. All cell lines showed at least 90% identical short tandem repeats. Moreover, microarray CGH analysis of DNA extracted from frozen tumor tissue of the primary tumor from which the cell lines were derived, showed an identical pattern of copy number alterations (Figure 3), although the amplitude of the observed gains and losses was higher in the cell lines.

Bottom Line: Overexpression of p53 was observed in five, and of EGFR in four cell lines.None of the cell lines showed strong immunopositivity of p16 or presence of human papilloma virus.In conclusion, we have created six new cell lines that are clinically and genetically representative of sinonasal SCC and that will be a useful tool for the preclinical testing of new therapeutic agents.

View Article: PubMed Central - PubMed

Affiliation: Dept. Otolaryngology, IUOPA, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.

ABSTRACT
Sinonasal squamous cell carcinomas (SCC) are rare tumors, etiologically related to occupational exposure to wood and leather dust. In spite of surgical and radiotherapeutic advances, the 5 year survival is still 30-50%. Therefore, alternative treatment options are needed. We report the establishment and characterization of six unique human sinonasal SCC cell lines, named SCCNC1, 2, 4, 5, 6 and 7. In vitro growth and invasion characteristics were evaluated and genetic profiles were compared to those of the original primary tumors. The population doubling times ranged from 21 to 34 hours. Cell lines SCCNC2 and 7 were highly invasive in matrigel. Five cell lines carried a high number of copy number alterations, including amplifications and homozygous deletions, while one showed only three abnormalities. Sequence analysis revealed three cell lines with TP53 mutation and none with KRAS or BRAF. Overexpression of p53 was observed in five, and of EGFR in four cell lines. None of the cell lines showed strong immunopositivity of p16 or presence of human papilloma virus. In conclusion, we have created six new cell lines that are clinically and genetically representative of sinonasal SCC and that will be a useful tool for the preclinical testing of new therapeutic agents.

Show MeSH
Related in: MedlinePlus