Mapping the in vivo fitness landscape of lung adenocarcinoma tumor suppression in mice

Zoë N Rogers; Christopher D McFarland; Ian P Winters; Jose A Seoane; Jennifer J Brady; Stephanie Yoon; Christina Curtis; Dmitri A Petrov; Monte M Winslow

doi:10.1038/s41588-018-0083-2

Mapping the in vivo fitness landscape of lung adenocarcinoma tumor suppression in mice

Nat Genet. 2018 Apr;50(4):483-486. doi: 10.1038/s41588-018-0083-2. Epub 2018 Apr 2.

Authors

Zoë N Rogers^#¹, Christopher D McFarland^#², Ian P Winters¹, Jose A Seoane^{1

3

4}, Jennifer J Brady¹, Stephanie Yoon⁵, Christina Curtis^{1

3

4

6}, Dmitri A Petrov⁷, Monte M Winslow^{8

9

10

11}

Affiliations

¹ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Biology, Stanford University, Stanford, CA, USA.
³ Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, USA.
⁴ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁶ Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Department of Biology, Stanford University, Stanford, CA, USA. [email protected].
⁸ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
⁹ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
¹⁰ Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
¹¹ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. [email protected].

^# Contributed equally.

Abstract

The functional impact of most genomic alterations found in cancer, alone or in combination, remains largely unknown. Here we integrate tumor barcoding, CRISPR/Cas9-mediated genome editing and ultra-deep barcode sequencing to interrogate pairwise combinations of tumor suppressor alterations in autochthonous mouse models of human lung adenocarcinoma. We map the tumor suppressive effects of 31 common lung adenocarcinoma genotypes and identify a landscape of context dependence and differential effect strengths.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung / genetics*
Animals
CRISPR-Cas Systems
DNA Barcoding, Taxonomic
Gene Deletion
Gene Editing
Genes, Tumor Suppressor*
Genes, p53
Genetic Fitness
High-Throughput Nucleotide Sequencing
Humans
Lung Neoplasms / genetics*
Mice
Mice, Transgenic
Retinoblastoma Protein / genetics
Sequence Analysis, DNA

Substances

Retinoblastoma Protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding