Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions

Nature Communications
Martin G DalinLuc G T Morris

Abstract

Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which is associated with PLAG1 overexpression. We find FGFR1-PLAG1 in seven (18%) cases, and the novel TGFBR3-PLAG1 fusion in six (15%) cases. TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 other salivary gland tumors. Other novel PLAG1 fusions include ND4-PLAG1; a fusion between mitochondrial and nuclear DNA. We also identify higher number of copy number alterations as a risk factor for recurrence, independent of tumor stage at diagnosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal cancer.

References

Jun 8, 2000·The American Journal of Surgical Pathology·A T SaveraD S Klimstra
Nov 25, 2004·European Journal of Oral Sciences·Fredrik EnlundGöran Stenman
Jun 3, 2005·Cancer Research·Jeroen DeclercqWim J M Van de Ven
Aug 2, 2005·Cancer Letters·Sue RutherfordChristopher A Moskaluk
Oct 26, 2006·Journal of Cellular Physiology·Abbas Abdollahi
Dec 16, 2006·Genes, Chromosomes & Cancer·Lurdes QueimadoAntonio M C Reis
Nov 16, 2007·Nature Reviews. Cancer·Alfredo Fusco, Monica Fedele
Jul 8, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Karolin H HallorFredrik Mertens
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jan 14, 2010·Genome Biology·Kumaran KandasamyAkhilesh Pandey
Mar 12, 2011·Virchows Archiv : an International Journal of Pathology·Atsuji MatsuyamaHiroshi Hashimoto
Apr 13, 2011·Genes, Chromosomes & Cancer·Cristina R AntonescuIlan Weinreb
Jun 1, 2011·PLoS Computational Biology·Andrew McPhersonSohrab P Shah
Aug 19, 2011·Neoplasia : an International Journal for Oncology Research·Catherine E GatzaGerard C Blobe
Dec 14, 2011·Human Pathology·Uta FluckeBastiaan B J Tops
May 15, 2012·Bioinformatics·Christopher T SaundersR Keira Cheetham
Oct 30, 2012·American Journal of Human Genetics·Goo JunHyun Min Kang
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Dec 12, 2012·Genome Medicine·René L WarrenRobert A Holt
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz
May 21, 2013·Nature Genetics·Allen S HoTimothy A Chan
Jun 4, 2013·The New England Journal of Medicine·Alice T ShawPasi A Jänne
Jun 6, 2013·Genes, Chromosomes & Cancer·Cristina R AntonescuChristopher D M Fletcher
Jul 4, 2013·Head and Neck Pathology·Göran Stenman
Oct 12, 2013·Advances in Anatomic Pathology·Ilan Weinreb
Mar 19, 2014·Nature Methods·Andrew RothSohrab P Shah
Aug 12, 2014·Fertility and Sterility·Miika MehinePia Vahteristo
Nov 20, 2014·The New England Journal of Medicine·Alexandra SnyderTimothy A Chan
Jan 30, 2015·Nature·UNKNOWN Cancer Genome Atlas Network

❮ Previous
Next ❯

Citations

Apr 25, 2018·Drug Metabolism and Personalized Therapy·Sujit Nair, Adrián LLerena
Oct 5, 2018·The American Journal of Surgical Pathology·Lisa M RooperJustin A Bishop
Feb 28, 2019·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Simon AndreasenIrene Wessel
Mar 23, 2019·Expert Opinion on Investigational Drugs·Stefano CavalieriSalvatore Alfieri
Feb 23, 2019·The American Journal of Surgical Pathology·Bin XuNora Katabi
Apr 4, 2020·International Journal of Surgical Pathology·Zhenjian CaiHui Zhu
Apr 24, 2019·Nature Medicine·Wei YangLuc G T Morris
Nov 26, 2020·Virchows Archiv : an International Journal of Pathology·Hanna MajewskaWojciech Biernat
Feb 16, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maximilian LinxweilerLuc G T Morris
Dec 11, 2020·Genes, Chromosomes & Cancer·Catherine T ChungPaul S Thorner
Feb 3, 2021·Surgical Pathology Clinics·Bin Xu, Nora Katabi
Feb 3, 2021·Surgical Pathology Clinics·Doreen PalsgroveSaad A Khan
Jan 7, 2021·Advances in Anatomic Pathology·M Hasan Toper, Sulen Sarioglu
Mar 18, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Yajuan J LiuEleanor Y Chen
Apr 21, 2021·Neoplasia : an International Journal for Oncology Research·Sandra N FreibergerNiels J Rupp
Jun 28, 2021·Genes, Chromosomes & Cancer·Justin BubolaBrendan C Dickson

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
PCR
exome seq
Feature Extraction
FACS

Software Mentioned

Burrows
FusionCatcher
Isis
Varscan
FASST2
NetMHC
DeSeq2
STAR aligner
Integrative Genomics Viewer ( IGV )
Nexus Copy Number

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.