Genomic Profiling of Advanced-Stage, Metaplastic Breast Carcinoma by Next-Generation Sequencing Reveals Frequent, Targetable Genomic Abnormalities and Potential New Treatment Options

If you need an accessible version of this item, please email your request to digschol@iu.edu so that they may create one and provide it to you.
Date
2015-05
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
Abstract

Context.— Metastatic metaplastic breast carcinoma (MPBC) is an uncommon, but aggressive, tumor resistant to conventional chemotherapy.

Objective.— To learn whether next-generation sequencing could identify potential targets of therapy for patients with relapsed and metastatic MPBC.

Design.— Hybridization capture of 3769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to a minimum of 50 ng of DNA extracted from 20 MPBC formalin-fixed, paraffin-embedded specimens and sequenced to high uniform coverage.

Results.— The 20 patients with MPBC had a median age of 62 years (range, 42–86 years). There were 9 squamous (45%), 9 chondroid (45%), and 2 spindle cell (10%) MPBCs, all of which were high grade. Ninety-three genomic alterations were identified, (range, 1–11) with 19 of the 20 cases (95%) harboring an alteration that could potentially lead to a targeted treatment option. The most-common alterations were in TP53 (n = 69; 75%), PIK3CA (n = 37; 40%), MYC (n = 28; 30%), MLL2 (n = 28; 30%), PTEN (n = 23; 25%), CDKN2A/B (n = 19; 20%), CCND3 (n = 14; 15%), CCNE1 (n = 9; 10%), EGFR (n = 9; 10%), and KDM6A (n = 9; 10%); AKT3, CCND1, CCND2, CDK4, FBXW7, FGFR1, HRAS, NF1, PIK3R1, and SRC were each altered in a single case. All 16 MPBCs (100%) that were negative for ERBB2 (HER2) overexpression by immunohistochemistry and/or ERBB2 (HER2) amplification by fluorescence in situ hybridization were also uniformly (100%) negative for ERBB2 amplification by next-generation sequencing–based copy-number assessment.

Conclusions.— Our results indicate that genomic profiling using next-generation sequencing can identify clinically meaningful alterations that have the potential to guide targeted treatment decisions in most patients with metastatic MPBC.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Ross, J. S., Badve, S., Wang, K., Sheehan, C. E., Boguniewicz, A. B., Otto, G. A., ... & Stephens, P. J. (2015). Genomic profiling of advanced-stage, metaplastic breast carcinoma by next-generation sequencing reveals frequent, targetable genomic abnormalities and potential new treatment options. Archives of pathology & laboratory medicine, 139(5), 642.
ISSN
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Archives of Pathology & Laboratory Medicine
Source
Publisher
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Final published version
Full Text Available at
This item is under embargo {{howLong}}