Molecular and genomic characterisation of a panel of human anal cancer cell lines

Guerra, Glen R. and Kong, Joseph C. and Millen, Rosemary M. and Read, Matthew and Liu, David S. and Roth, Sara and Sampurno, Shienny and Sia, Joseph and Bernardi, Maria-Pia and Chittleborough, Timothy J. and Behrenbruch, Corina C. and Teh, Jiasian and Xu, Huiling and Haynes, Nicole M. and Yu, Jiaan and Lupat, Richard and Hawkes, David and Di Costanzo, Natasha and Tothill, Richard W. and Mitchell, Catherine and Ngan, Samuel Y. and Heriot, Alexander G. and Ramsay, Robert G. and Phillips, Wayne A. (2021) Molecular and genomic characterisation of a panel of human anal cancer cell lines. Cell Death & Disease, 12 (11). ISSN 2041-4889, DOI

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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.

Item Type: Article
Funders: National Health and Medical Research Council (NHMRC) of Australia, Royal Australasian College of Surgeons (RACS) Tour De Cure Scholarship, RACS Foundation for Surgery Research Scholarship, RACS ANZ Journal of Surgery Scholarship, Covidien Colorectal Research Fellowship, Cancer Therapeutics Research Scholarship (Cancer Therapeutics CRC)
Uncontrolled Keywords: Carcinoma; Mutations; Pembrolizumab; Expression; Signatures; framework; Reveals; Marker
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Medicine > Pathology Department
Depositing User: Ms Zaharah Ramly
Date Deposited: 14 Sep 2022 00:51
Last Modified: 14 Sep 2022 00:51

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