Abstract LB290: Whole exome analysis of oral squamous cell carcinoma in local patients at tertiary care hospitals in Peshawar, Pakistan
Authors: Zamir Hina , Salim Khudeja , Sherdil Madina , Hussain Aqsa , Ilyas Yusra , Riaz Arsalan , Agha Momal , Jahan Zainab , Shah Khadim , Khattak Yasir Rehman , Uddin Fahim , Shah Zahid Qayyum , Durrani Zubair , Khattak Muhammad Mushtaq , Ali Johar , Khan Faisal F. 
Published: April 2024

The Precision Medicine Lab (PML) has been mandated by the Federal Government in 2018 to pilot precision medicine in Pakistan using genomics in oral cancer. With the Indian subcontinent as its capital, oral squamous cell carcinoma (OSCC), also dubbed as ‘poor man’s cancer', constitutes 90% of all head and neck cancers and is the highest incidence cancer found in Pakistani males. Backed by a bio-repository of clinical samples as well as a catalogue of primary cell clines, PML takes a multi-omic approach to discovering new, actionable biomarkers for diagnostic, prognostic and therapeutic applications.

With all necessary ethical approvals obtained from IRBs at each site along with written informed consent from each patient, treatment-naive biopsy-confirmed patients of OSCC were recruited in two main tertiary care hospitals in Peshawar, Pakistan. Our cohort was predominantly older with 37.84% between 41-60 years, late-stage with 78.46% presenting in stage IV and self-reportedly non-alcohol consuming (96.9%). About 44.6% reported the use of smokeless tobacco while 30.8% reported the use of both smoked and smokeless tobacco. Majority of the tumours were located in the buccal mucosa (29.2%), alveolar region (27.7%) or the vestibular region (24.6%). We obtained blood and tumour samples for matched-pair whole exome sequencing, transcriptomics and metabolomics as well as generation of primary cell lines. We also obtained saliva samples for oral microbiome analysis. Combined with the patient’s clinical history and digital histopathology images, this helps us create a multi-omic stack that we intend to make available for integrated machine learning experiments.

With our whole exome sequencing now complete, we undertook a preliminary analysis for this late breaking abstract. Raw reads were aligned to the GRCh38.p14 reference genome and were called for germline and somatic SNPs and INDELs using GATK (v4.5). Mutational analysis was conducted using the maftools (v2.18.0) package in R (v4.3) by comparing against the COSMIC SBS Signature database (v3.2). We report MUC12 (100%), ZNF717 (100%), FOLR3 (86%), EPPK1 (79%) and SPATA31A6 (79%) as the top mutated genes in the subset of exomes analysed thus far for our cohort. Genes reported previously including TP53, NOTCH1 and PIK3CA appear to rank lower on the list. In terms of cancer-related pathways, RTK-RAS (92.8%), Hippo (92.8%) and Notch (78.5%) were affected in most of the samples.

To our knowledge, we describe for the first time the mutational landscape in an OSCC cohort from the Pakistani population. We also go beyond whole exomes as our multi-omic approach offers the potential on machine learning experiments to identify putative mutational signatures and biomarkers for OSCC that can be of diagnostic, prognostic and therapeutic value to the local (Pakistani and Afghan) patient population. With the availability of primary cell lines for every patient, we also intend to undertake experimental validation of high priority targets using primary patient-derived cell lines in the lab.

Citation Format: Hina Zamir, Khudeja Salim, Madina Sherdil, Aqsa Hussain, Yusra Ilyas, Arsalan Riaz, Momal Agha, Zainab Jahan, Khadim Shah, Yasir Rehman Khattak, Fahim Uddin, Zahid Qayyum Shah, Zubair Durrani, Muhammad Mushtaq Khattak, Johar Ali, Faisal F. Khan. Whole exome analysis of oral squamous cell carcinoma in local patients at tertiary care hospitals in Peshawar, Pakistan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB290.