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

Author:

Guerra Glen R.ORCID,Kong Joseph C.,Millen Rosemary M.,Read Matthew,Liu David S.,Roth Sara,Sampurno Shienny,Sia Joseph,Bernardi Maria-Pia,Chittleborough Timothy J.,Behrenbruch Corina C.,Teh Jiasian,Xu Huiling,Haynes Nicole M.,Yu Jiaan,Lupat Richard,Hawkes David,Di Costanzo Natasha,Tothill Richard W.,Mitchell Catherine,Ngan Samuel Y.,Heriot Alexander G.,Ramsay Robert G.ORCID,Phillips Wayne A.ORCID

Abstract

AbstractAnal 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.

Funder

Department of Health | National Health and Medical Research Council

Royal Australasian College of Surgeons

Covidien Colorectal Research Fellowship and Cancer Therapeutics Research Scholarship

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology

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