Transcriptomes define distinct subgroups of salivary gland adenoid cystic carcinoma with different driver mutations and outcomes

Oncotarget
Candace A FrerichScott A Ness

Abstract

The relative rarity of salivary gland adenoid cystic carcinoma (ACC) and its slow growing yet aggressive nature has complicated the development of molecular markers for patient stratification. To analyze molecular differences linked to the protracted disease course of ACC and metastases that form 5 or more years after diagnosis, detailed RNA-sequencing (RNA-seq) analysis was performed on 68 ACC tumor samples, starting with archived, formalin-fixed paraffin-embedded (FFPE) samples up to 25 years old, so that clinical outcomes were available. A statistical peak-finding approach was used to classify the tumors that expressedMYBorMYBL1, which had overlapping gene expression signatures, from a group that expressed neither oncogene and displayed a unique phenotype. Expression ofMYBorMYBL1was closely correlated to the expression of theSOX4andEN1genes, suggesting that they are direct targets of Myb proteins in ACC tumors. Unsupervised hierarchical clustering identified a subgroup of approximately 20% of patients with exceptionally poor overall survival (median less than 30 months) and a unique gene expression signature resembling embryonic stem cells. The results provide a strategy for stratifying ACC patients and identifying the high-...Continue Reading

References

Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·V G TusherG Chu
Jun 5, 2002·Genome Research·W James KentDavid Haussler
Oct 9, 2002·The American Journal of Pathology·Henry F FriersonGarret M Hampton
Apr 24, 2004·The Journal of Biological Chemistry·Wanli LeiScott A Ness
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jan 16, 2008·Molecular and Cellular Biology·John P O'Rourke, Scott A Ness
Apr 23, 2008·Current Protocols in Bioinformatics·Donna KarolchikW James Kent
Jun 25, 2008·Nature Reviews. Cancer·Robert G Ramsay, Thomas J Gonda
Oct 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Marta PerssonGöran Stenman
Aug 13, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yoshitsugu MitaniAdel K El-Naggar
Jan 5, 2011·Frontiers in Bioscience (Landmark Edition)·Ye Zhou, Scott A Ness
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
May 17, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Louis B BrillHenry F Frierson
Aug 27, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mei ZhaoJeffrey N Myers
Oct 7, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yoshitsugu MitaniAdel K El-Naggar
Nov 23, 2011·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Chenchen ZhouXinhua Liang
Dec 1, 2011·Statistical Methods in Medical Research·Jun Li, Robert Tibshirani
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Feb 19, 2013·Molecular Oncology·Karen GambaroPatricia N Tonin
Jul 3, 2013·Methods : a Companion to Methods in Enzymology·Matthew P A DavisAnton J Enright
Mar 4, 2014·Genome Biology·Derrick E Wood, Steven L Salzberg
Dec 10, 2014·Head & Neck·Patrick M DillonChristopher Y Thomas
Jan 1, 2015·Journal of Experimental & Clinical Cancer Research : CR·Xin ZhuMing-hua Ge
Dec 4, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yoshitsugu MitaniAdel El-Naggar

❮ Previous
Next ❯

Citations

Aug 3, 2018·Virchows Archiv : an International Journal of Pathology·Simon AndreasenPreben Homøe
Sep 5, 2019·The Journal of Clinical Investigation·Allen S HoLuc Gt Morris
Jun 21, 2018·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Simon Andreasen
Nov 12, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Renata FerrarottoAdel K El-Naggar
Feb 3, 2021·Surgical Pathology Clinics·Doreen PalsgroveSaad A Khan
Jun 28, 2021·Genes, Chromosomes & Cancer·Justin BubolaBrendan C Dickson

❮ Previous
Next ❯

Datasets Mentioned

BETA
PRJNA287156

Methods Mentioned

BETA
RNA-seq
PCR
transfection
ChIP-seq
ChIP
HT-Seq
PCA
Transfections
Assay

Software Mentioned

R
Gene Set Enrichment Analysis
Integrative Genomics Viewer
package stats
HOMER
UCSC genome browser
samr R
STAR
BLAT
Bioconductor

Related Concepts

Related Feeds

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.