American Association for Cancer Research
15417786mcr170060-sup-178149_2_supp_4172604_jtjkjp.docx (19.95 kB)

Supplemental Methods from Comprehensive Genomic Profiling of Metastatic Squamous Cell Carcinoma of the Anal Canal

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journal contribution
posted on 2023-04-03, 16:21 authored by Van Morris, Xiayu Rao, Curtis Pickering, Wai Chin Foo, Asif Rashid, Karina Eterovic, Taebeom Kim, Ken Chen, Jing Wang, Kenna Shaw, Cathy Eng

Genomic DNA: library prep and capture.


University of Texas MD Anderson Cancer Center



Squamous cell carcinoma of the anal canal (SCCA) is a rare gastrointestinal malignancy with an increasing annual incidence globally. The majority of cases are linked to prior infection with the human papillomavirus (HPV). For patients with metastatic SCCA, no consensus standard treatment exists. Identification of relevant targeted agents as novel therapeutic approaches for metastatic SCCA has been limited by a lack of comprehensive molecular profiling. We performed whole-exome sequencing on tumor–normal pairs from 24 patients with metastatic SCCA. Tumor tissue from 17 additional patients was analyzed using a 263-gene panel as a validation cohort. Gene expression profiling was performed on available frozen tissue to assess for differential expression patterns. Based on these findings, patient-derived xenograft (PDX) models of SCCA were generated to test targeted therapies against PI3K and EGFR. Despite a low mutation burden, mutations in PIK3CA, MLL2, and MLL3 were among the most commonly mutated genes. An association between TP53 mutations and HPV-negative SCCA tumors was observed. Gene expression analysis suggested distinct tumor subpopulations harboring PIK3CA mutations and for which HPV had integrated into the host genome. In vivo studies demonstrated improvement with anti-EGFR treatment. Gene mutation frequencies, tumor mutation burden, and gene expression patterns for metastatic SCCA appear similar to other HPV-associated malignancies.Implications: This first comprehensive genomic characterization for patients with metastatic SCCA provides further rationale for the integration of SCCA into the development of novel targeted therapies across HPV-related cancers. Mol Cancer Res; 15(11); 1542–50. ©2017 AACR.

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