Supplementary Tables from Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers

Lui, Vivian W.Y.; Hedberg, Matthew L.; Li, Hua; Vangara, Bhavana S.; Pendleton, Kelsey; Zeng, Yan; Lu, Yiling; Zhang, Qiuhong; Du, Yu; Gilbert, Breean R.; Freilino, Maria; Sauerwein, Sam; Peyser, Noah D.; Xiao, Dong; Diergaarde, Brenda; Wang, Lin; Chiosea, Simion; Seethala, Raja; Johnson, Jonas T.; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L.; Romkes, Marjorie; Nukui, Tomoko; Kwok-Shing Ng, Patrick; Garraway, Levi A.; Hammerman, Peter S.; Mills, Gordon B.; Grandis, Jennifer R.

doi:10.1158/2159-8290.22529964.v1

Supplementary Tables from Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers

journal contribution

posted on 2023-04-03, 20:43 authored by Vivian W.Y. Lui, Matthew L. Hedberg, Hua Li, Bhavana S. Vangara, Kelsey Pendleton, Yan Zeng, Yiling Lu, Qiuhong Zhang, Yu Du, Breean R. Gilbert, Maria Freilino, Sam Sauerwein, Noah D. Peyser, Dong Xiao, Brenda Diergaarde, Lin Wang, Simion Chiosea, Raja Seethala, Jonas T. Johnson, Seungwon Kim, Umamaheswar Duvvuri, Robert L. Ferris, Marjorie Romkes, Tomoko Nukui, Patrick Kwok-Shing Ng, Levi A. Garraway, Peter S. Hammerman, Gordon B. Mills, Jennifer R. Grandis

Supplementary Tables - PDF file 207K, Five supplementary tables denoting clinical characteristics of tumors, statistical correlations between PI3K mutational status, HPV status, cancer gene mutation status, and significance of pathway and gene mutation rates compared to background mutation rates, normalized to bases covered by exome sequencing

History

ARTICLE ABSTRACT

Genomic findings underscore the heterogeneity of head and neck squamous cell carcinoma (HNSCC). Identification of mutations that predict therapeutic response would be a major advance. We determined the mutationally altered, targetable mitogenic pathways in a large HNSCC cohort. Analysis of whole-exome sequencing data from 151 tumors revealed the phosphoinositide 3-kinase (PI3K) pathway to be the most frequently mutated oncogenic pathway (30.5%). PI3K pathway–mutated HNSCC tumors harbored a significantly higher rate of mutations in known cancer genes. In a subset of human papillomavirus-positive tumors, PIK3CA or PIK3R1 was the only mutated cancer gene. Strikingly, all tumors with concurrent mutation of multiple PI3K pathway genes were advanced (stage IV), implicating concerted PI3K pathway aberrations in HNSCC progression. Patient-derived tumorgrafts with canonical and noncanonical PIK3CA mutations were sensitive to an mTOR/PI3K inhibitor (BEZ-235), in contrast to PIK3CA–wild-type tumorgrafts. These results suggest that PI3K pathway mutations may serve as predictive biomarkers for treatment selection.Significance: Treatment options for HNSCC are limited, in part, because of an incomplete understanding of the targetable mutations that “drive” tumor growth. Here, we define a subgroup of HNSCC harboring activating mutations of genes in the PI3K pathway where targeting the pathway shows antitumor efficacy. These results suggest that PI3K pathway mutation assessment may be used to guide HNSCC therapy. Cancer Discov; 3(7); 761–9. ©2013 AACR.See related commentary by Iglesias-Bartolome et al., p. 722This article is highlighted in the In This Issue feature, p. 705