The association of genomic lesions and PD-1/PD-L1 expression in resected triple-negative breast cancers

Breast Cancer Research : BCR
Michael T BarrettBarbara A Pockaj

Abstract

Elevated PD-L1 expression on tumor cells, a context associated with an adaptive immune response, has been linked to the total burden of copy number variants (CNVs) in aneuploid tumors, to microsatellite instability (MSI), and to specific genomic driver lesions, including loss of PTEN, MYC amplification, and activating mutations in driver oncogenes such as KRAS and PIK3CA. Triple-negative breast cancers (TNBCs) typically have high levels of CNVs and diverse driver lesions in their genomes. Thus, there is significant interest in exploiting genomic data to develop predictive immunotherapy biomarkers for patients with TNBC. Whole tissue samples from 55 resected TNBCs were screened by immunohistochemistry (IHC) for PD-1 and PD-L1 by using validated antibodies and established scoring methods for staining of tumor and non-tumor cells. In parallel, we interrogated biopsies from each resection with DNA content flow cytometry and sorted the nuclei of diploid, tetraploid, and aneuploid cell populations. CNVs were mapped with CNV oligonucleotide arrays by using purified (>95%) tumor populations. We generated whole exome data for 12 sorted tumor samples to increase the resolution within loci of interest and to incorporate somatic mutations ...Continue Reading

References

Nov 28, 2001·The American Journal of Gastroenterology·P S RabinovitchB J Reid
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Apr 7, 2006·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Doron LipsonZohar Yakhini
Nov 13, 2009·Nucleic Acids Research·Randi VitaBjoern Peters
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Christian RuizMichael T Barrett
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Dec 12, 2012·PloS One·Tara HolleyMichael T Barrett
Feb 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jacky T YeungHideho Okada
Jun 4, 2013·The New England Journal of Medicine·Jedd D WolchokMario Sznol
Nov 19, 2013·Nature Structural & Molecular Biology·Sugiko WatanabeJiri Bartek
Feb 20, 2014·PloS One·Hatem SolimanScott Antonia
Apr 10, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Janis M TaubeRobert A Anders
Apr 26, 2014·Cancer Immunology Research·Elizabeth A MittendorfGheath Alatrash
Jul 11, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K AzumaI Okamoto
Aug 1, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Jul 15, 2015·The Journal of Biological Chemistry·Bogdan I FedelesJohn M Essigmann
Aug 13, 2015·Nature·Shany KorenMohamed Bentires-Alj
Sep 16, 2015·Nature Biotechnology·Sachet A ShuklaGad Getz
Sep 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesco SabbatinoCristina R Ferrone
Dec 1, 2015·Nature Medicine·Noemi AndorCarlo C Maley
Dec 10, 2015·Cancer Discovery·Weiyi PengPatrick Hwu
Jan 15, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Seiichi IkedaYoshihiko Maehara
Mar 27, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Masaki MandaiIkuo Konishi
Apr 15, 2016·Science Translational Medicine·Justin M BalkoCarlos L Arteaga
Apr 16, 2016·Nature Reviews. Cancer·Suzanne L TopalianDrew M Pardoll
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Jul 20, 2016·The New England Journal of Medicine·Jesse M ZaretskyAntoni Ribas
Sep 14, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Julie GeorgeTakashi Kohno
Oct 11, 2016·The New England Journal of Medicine·Martin ReckUNKNOWN KEYNOTE-024 Investigators
Dec 3, 2016·Cancer Discovery·Daniel Sanghoon ShinAntoni Ribas
Dec 30, 2016·Cancer Discovery·Valsamo AnagnostouVictor E Velculescu
Jul 20, 2017·British Journal of Cancer·Michael T BarrettDaniel D Von Hoff
Jul 29, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Meixuan ChenKaren S Anderson
Aug 8, 2017·Nature·Shashank J PatelNicholas P Restifo

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Citations

Mar 15, 2019·PloS One·Michael T BarrettAlan H Bryce
May 8, 2020·Journal of the National Comprehensive Cancer Network : JNCCN·Saranya ChumsriE Aubrey Thompson
Feb 1, 2020·Journal of Translational Medicine·Vildan B Cetintas, Nizar N Batada
Jul 31, 2019·Breast Cancer Research and Treatment·Wenfa HuangHuiping Li
Jun 23, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexios MatikasTheodoros Foukakis
Dec 31, 2019·Seminars in Cancer Biology·Semir VranicJuan Palazzo
Dec 15, 2020·Cancer Medicine·Abirami SivapiragasamJeffrey S Ross
Jun 20, 2021·International Immunopharmacology·Melina FarshbafnadiNima Rezaei
Jun 26, 2021·Radiology. Imaging Cancer·Tobias BäuerleAlexei Bogdanov
Jun 30, 2021·Journal of Cancer Research and Clinical Oncology·Karen BräutigamFrank Köster

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Datasets Mentioned

BETA
GSE107764

Methods Mentioned

BETA
surgical resections
flow cytometry
biopsies
Feature Extraction
exome sequencing
biopsy
flow

Software Mentioned

Illumina
MultiCycle
Annovar
RTA
fasta
VarScan2
POLYSOLVER
Agilent Feature Extraction
SAS

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