Skip to main content

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

Publication ,  Journal Article
Wagner, AH; Devarakonda, S; Skidmore, ZL; Krysiak, K; Ramu, A; Trani, L; Kunisaki, J; Masood, A; Waqar, SN; Spies, NC; Morgensztern, D; Can, I ...
Published in: Nat Commun
September 17, 2018

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

September 17, 2018

Volume

9

Issue

1

Start / End Page

3787

Location

England

Related Subject Headings

  • Wnt Signaling Pathway
  • Small Cell Lung Carcinoma
  • Neoplasm Recurrence, Local
  • Mutation
  • Lung Neoplasms
  • Loss of Heterozygosity
  • Humans
  • Gene Knockdown Techniques
  • Gene Expression Regulation, Neoplastic
  • Exome Sequencing
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wagner, A. H., Devarakonda, S., Skidmore, Z. L., Krysiak, K., Ramu, A., Trani, L., … Govindan, R. (2018). Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer. Nat Commun, 9(1), 3787. https://doi.org/10.1038/s41467-018-06162-9
Wagner, Alex H., Siddhartha Devarakonda, Zachary L. Skidmore, Kilannin Krysiak, Avinash Ramu, Lee Trani, Jason Kunisaki, et al. “Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer.Nat Commun 9, no. 1 (September 17, 2018): 3787. https://doi.org/10.1038/s41467-018-06162-9.
Wagner AH, Devarakonda S, Skidmore ZL, Krysiak K, Ramu A, Trani L, et al. Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer. Nat Commun. 2018 Sep 17;9(1):3787.
Wagner, Alex H., et al. “Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer.Nat Commun, vol. 9, no. 1, Sept. 2018, p. 3787. Pubmed, doi:10.1038/s41467-018-06162-9.
Wagner AH, Devarakonda S, Skidmore ZL, Krysiak K, Ramu A, Trani L, Kunisaki J, Masood A, Waqar SN, Spies NC, Morgensztern D, Waligorski J, Ponce J, Fulton RS, Maggi LB, Weber JD, Watson MA, O’Conor CJ, Ritter JH, Olsen RR, Cheng H, Mukhopadhyay A, Can I, Cessna MH, Oliver TG, Mardis ER, Wilson RK, Griffith M, Griffith OL, Govindan R. Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer. Nat Commun. 2018 Sep 17;9(1):3787.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

September 17, 2018

Volume

9

Issue

1

Start / End Page

3787

Location

England

Related Subject Headings

  • Wnt Signaling Pathway
  • Small Cell Lung Carcinoma
  • Neoplasm Recurrence, Local
  • Mutation
  • Lung Neoplasms
  • Loss of Heterozygosity
  • Humans
  • Gene Knockdown Techniques
  • Gene Expression Regulation, Neoplastic
  • Exome Sequencing