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Increased RNA Expression of von Willebrand Factor Gene Is Associated With Infiltrating Lobular Breast Cancer and Normal PAM50 Subtype.

Authors
  • Lehrer, Steven1
  • Green, Sheryl2
  • Dembitzer, Francine R3
  • Rheinstein, Peter H4
  • Rosenzweig, Kenneth E2
  • 1 Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A [email protected]
  • 2 Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A.
  • 3 Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A.
  • 4 Severn Health Solutions, Severna Park, MD, U.S.A.
Type
Published Article
Journal
Cancer Genomics & Proteomics
Publisher
International Institute of Anticancer Research
Publication Date
Jan 01, 2019
Volume
16
Issue
3
Pages
147–153
Identifiers
DOI: 10.21873/cgp.20120
PMID: 31018945
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Infiltrating lobular carcinoma (ILC) is the second most common histologicaI subtype of breast cancer, accounting for 10% of all cases. ILC has a characteristic genomic profile. ILC shows a high frequency of cadherin 1 (CDH1) mutations, along with loss of phosphatase and tensin homolog (PTEN), activation of alpha serine/threonine kinase (AKT), and mutations in T-box transcription factor (TBX3) and forkhead box protein A1 (FOXA1). We suspected that another gene, von Willebrand factor (VWF), might also be part of the profile, since coagulation tests reveal significant differences in patients with breast cancer. For newly-diagnosed breast cancer, the association between VWF and histology in the GDC Breast Cancer dataset in The Cancer Genome Atlas (TCGA) was evaluated. The following were used to access and analyze the data: Genomic Data Commons Data Portal (https://portal.gdc.cancer.gov/); Xena browser (https://xenabrowser.net); cBioportal (http://cbioportal.org); Oncomine (https://oncomine.org); and Prediction Analysis of Microarray 50 (PAM50). Patients with ILC had higher VWF RNA expression than patients with infiltrating ductal carcinoma and other histology. The difference of expression was present to the same degree in both pre-menopausal and post-menopausal patients. Nine alterations in VWF and PTEN were significantly co-occurrent. Considering all histologies in 843 samples, Tukey's honest significant difference post hoc test showed that VWF RNA expression of the normal subtype was significantly greater than that of the other subtypes (p<0.001). Our finding of significantly higher VWF RNA expression in the PAM50 normal (non-basal-like) breast cancer subtype suggests that VWF protein measurement might complement or corroborate PAM50 results. VWF and PAM50 results both suggesting a low risk of recurrence might make the decision whether to give chemotherapy easier, especially if VWF protein were an independent predictor. Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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