Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer

Nature Communications
Alex H WagnerRamaswamy Govindan

Abstract

Nearly all patients with small cell lung cancer (SCLC) eventually relapse with chemoresistant disease. The molecular mechanisms driving chemoresistance in SCLC remain un-characterized. Here, we describe whole-exome sequencing of paired SCLC tumor samples procured at diagnosis and relapse from 12 patients, and unpaired relapse samples from 18 additional patients. Multiple somatic copy number alterations, including gains in ABCC1 and deletions in MYCL, MSH2, and MSH6, are identifiable in relapsed samples. Relapse samples also exhibit recurrent mutations and loss of heterozygosity in regulators of WNT signaling, including CHD8 and APC. Analysis of RNA-sequencing data shows enrichment for an ASCL1-low expression subtype and WNT activation in relapse samples. Activation of WNT signaling in chemosensitive human SCLC cell lines through APC knockdown induces chemoresistance. Additionally, in vitro-derived chemoresistant cell lines demonstrate increased WNT activity. Overall, our results suggest WNT signaling activation as a mechanism of chemoresistance in relapsed SCLC.

References

Mar 21, 2001·Human Molecular Genetics·N S FearnheadW F Bodmer
Sep 30, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ramaswamy GovindanJay Piccirillo
Jan 20, 2007·Bioinformatics·E S Venkatraman, Adam B Olshen
Dec 22, 2007·Nature Reviews. Immunology·Laurence ZitvogelGuido Kroemer
Apr 2, 2008·Molecular and Cellular Biology·Brandi A ThompsonDaniel A Bochar
Oct 7, 2008·Oncogene·S SegditsasI P M Tomlinson
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Dec 18, 2009·Nature·Erin D PleasancePeter J Campbell
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jynho KimPhilip A Beachy
Nov 16, 2011·Molecular and Cellular Biology·Masaaki NishiyamaKeiichi I Nakayama
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
May 15, 2012·Bioinformatics·Christopher T SaundersR Keira Cheetham
Jul 5, 2012·Genome Research·Nathan D DeesLi Ding
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Oct 23, 2014·Nature·Francisco J Sánchez-RiveraTyler Jacks
Dec 17, 2014·Neoplasia : an International Journal for Oncology Research·Nathan A DamaschkeDavid F Jarrard
Feb 19, 2015·Nature Biotechnology·Mihaela PerteaSteven L Salzberg
Mar 10, 2015·Nature Biotechnology·Alyssa C FrazeeJeffrey T Leek
Mar 10, 2015·Nature Methods·Daehwan KimSteven L Salzberg
Apr 22, 2015·Nucleic Acids Research·Damian SmedleyArek Kasprzyk
May 15, 2015·Nature·Stefani SprangerThomas F Gajewski
May 23, 2015·Cell·Dan RobinsonArul M Chinnaiyan
Jun 8, 2015·BMC Cancer·Monica K VanKlompenbergJenifer R Prosperi
Jul 15, 2015·PLoS Computational Biology·Malachi GriffithRichard K Wilson
Jul 15, 2015·Nature·Julie GeorgeRoman K Thomas

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Citations

Feb 1, 2020·Expert Opinion on Therapeutic Targets·Daniel Massó-VallésLaura Soucek
Oct 15, 2019·Frontiers in Immunology·Jesús Cosin-RogerMª Dolores Barrachina
Apr 14, 2020·Cell Biology International·Yuwen WangShi Xu
Dec 5, 2018·Nature Genetics·Jasreet HundalMalachi Griffith
Jul 14, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Siddhartha DevarakondaDaniel Morgensztern
Jun 6, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Milind D ChalishazarTrudy G Oliver
Jan 16, 2021·Nature Reviews. Disease Primers·Charles M RudinJulien Sage
Feb 6, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·John T PoirierTrudy G Oliver
Jun 10, 2020·Cold Spring Harbor Perspectives in Medicine·Benjamin J Drapkin, Charles M Rudin
Apr 8, 2021·Nature Communications·Christina M BebberSilvia von Karstedt
May 22, 2021·Communications Biology·Cody J ArosBrigitte N Gomperts
May 22, 2021·Genes & Development·Rachelle R OlsenTrudy G Oliver
Jun 25, 2021·Nature Communications·Nitin RoperAnish Thomas
Jun 26, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xuefeng LiHongbin Ji
Aug 7, 2021·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Brett H HerzogRamaswamy Govindan
Sep 11, 2021·Current Protocols·Zachary L SkidmoreObi L Griffith
Jan 9, 2022·Journal of Cancer Research and Clinical Oncology·Yamei ChenMing Chen

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Datasets Mentioned

BETA
OHu16786
U55763

Methods Mentioned

BETA
PCR
single-cell sequencing
xenografts
biopsy
biopsies
genotyping
transfection
RNA-seq

Software Mentioned

SciClone
Strelka
ssGSEA
GenePattern
Ensembl
Stringtie
Rad CFX Manager
Biomart
MuSiC
QIAGEN

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