Molecular and genomic characterisation of a panel of human anal cancer cell lines
| العنوان: | Molecular and genomic characterisation of a panel of human anal cancer cell lines |
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| المؤلفون: | Sara Roth, Richard Lupat, Natasha Di Costanzo, David Shi Hao Liu, Joseph C Kong, Huiling Xu, Matthew Read, David Hawkes, Jiaan Yu, Robert G. Ramsay, Shienny Sampurno, Wayne A. Phillips, Maria-Pia Bernardi, Joseph Sia, Rosemary Millen, Jiasian Teh, Richard W. Tothill, Glen R. Guerra, Nicole M. Haynes, Samuel Y Ngan, Corina Behrenbruch, Catherine Mitchell, Timothy J. Chittleborough, Alexander G. Heriot |
| المصدر: | Cell Death & Disease Cell Death and Disease, Vol 12, Iss 11, Pp 1-15 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Cancer Research, DNA Copy Number Variations, Carcinogenesis, medicine.medical_treatment, Xenotransplantation, Mitomycin, Immunology, Gene Dosage, Mice, Nude, Pembrolizumab, Major histocompatibility complex, B7-H1 Antigen, Article, Cellular and Molecular Neuroscience, Targeted therapies, Cell Line, Tumor, Spheroids, Cellular, MHC class I, medicine, Carcinoma, Anal cancer, Animals, Humans, Cancer models, Cell Proliferation, QH573-671, biology, Immune evasion, Histocompatibility Antigens Class I, Anal Squamous Cell Carcinoma, Cell Biology, Genomics, Middle Aged, medicine.disease, Anus Neoplasms, Xenograft Model Antitumor Assays, Radiation therapy, Mutation, Cancer research, biology.protein, Carcinoma, Squamous Cell, Female, Fluorouracil, Cytology |
| الوصف: | Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease. |
| تدمد: | 2041-4889 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2a541e01e752ebc28aa7d74c671318c https://pubmed.ncbi.nlm.nih.gov/34663790 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b2a541e01e752ebc28aa7d74c671318c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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