Science - USA (2022-05-27)

Janssen, AbbVie/Stemcentrx, Eli Lilly, Astellas, Millennium, and
Bristol Myers Squibb. F.T. is an employee at AbbVie, L.P.
is an employee at Loxo Oncology at Lilly, and K.E. is an employee
at Illumina. This work was completed prior to their employment
in industry. They are acting on their own, and these endeavors
are not in any manner affiliated with their current affiliations.
Data and materials availability:RNA-seq data for patients
sequenced at WCM are available at EGAS00001006059. ATAC-seq,
RNA-seq, and ChIP-seq data from cell lines, PDXs, and organoids are
available at Gene Expression Omnibus (GSE199190). MSK-IMPACT
mutational states can be found atwww.cbioportal.org. Code is

available at DOI: 10.5281/zenodo.5885500. New organoid models

reported in this work are available from Y.C. under a material transfer

agreement with Memorial Sloan Kettering Cancer Center.License

information:Copyright © 2022 the authors, some rights reserved;

exclusive licensee American Association for the Advancement of

Science. No claim to original US government works.www.science.org/

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SUPPLEMENTARY MATERIALS

science.org/doi/10.1126/science.abe1505

Materials and Methods

Supplementary Text

Figs. S1 to S25

Tables S1 to S17

References ( 51 – 79 )

MDAR Reproducibility Checklist

View/request a protocol for this paper fromBio-protocol.

Submitted 3 August 2020; resubmitted 18 September 2021

Accepted 20 April 2022

10.1126/science.abe1505

Tanget al., Science 376 , eabe1505 (2022) 27 May 2022 13 of 13

RESEARCH | RESEARCH ARTICLE