American Association for Cancer Research
Browse
- No file added yet -

Supplementary Figures from Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer

Download (1.13 MB)
journal contribution
posted on 2023-03-31, 19:29 authored by William J. Gibson, Daniel T. Ruan, Vera A. Paulson, Justine A. Barletta, Glenn J. Hanna, Stefan Kraft, Antonio Calles, Matthew A. Nehs, Francis D. Moore, Amaro Taylor-Weiner, Jeremiah A. Wala, Travis I. Zack, Thomas C. Lee, Fiona M. Fennessy, Erik K. Alexander, Tom Thomas, Pasi A. Janne, Levi A. Garraway, Scott L. Carter, Rameen Beroukhim, Jochen H. Lorch, Eliezer M. Van Allen

Supplementary Figure 1 The most frequent phylogenetic tree based on sampling mutations according to their detection power (276/1000 samples). Supplementary Figure 2 Allelic copy number profiles generated by ABSOLUTE (see Methods).

Funding

National Institute of General Medical Sciences

NIH

American Cancer Society

History

ARTICLE ABSTRACT

Purpose: Cancers may resist single-agent targeted therapies when the flux of cellular growth signals is shifted from one pathway to another. Blockade of multiple pathways may be necessary for effective inhibition of tumor growth. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR/PI3K or combined RAF/MEK inhibition but experienced a dramatic response when both drug regimens were combined.Experimental Design: Multi-region whole-exome sequencing of five diagnostic and four autopsy tumor biopsies was performed. Meta-analysis of DNA and RNA sequencing studies of ATC was performed.Results: Sequencing revealed truncal BRAF and PIK3CA mutations, which are known to activate the MAPK and PI3K/AKT pathways, respectively. Meta-analysis demonstrated 10.3% cooccurrence of MAPK and PI3K pathway alterations in ATC. These tumors display a separate transcriptional profile from other ATCs, consistent with a novel subgroup of ATC.Conclusions: BRAF and PIK3CA mutations define a distinct subset of ATC. Blockade of the MAPK and PI3K pathways appears necessary for tumor response in this subset of ATC. This identification of synergistic activity between targeted agents may inform clinical trial design in ATC. Clin Cancer Res; 23(9); 2367–73. ©2016 AACR.

Usage metrics

    Clinical Cancer Research

    Categories

    Keywords

    ChemotherapyCombination chemotherapyComputational MethodsGene expression profilingDna Damage And RepairGenomic instabilityEndocrine-Related Cancers

    Licence

    CC BY

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC