PMID- 35158935
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220219
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 3
DP  - 2022 Jan 28
TI  - An Integrated Epigenomic and Genomic View on Phyllodes and Phyllodes-like Breast 
      Tumors.
LID - 10.3390/cancers14030667 [doi]
LID - 667
AB  - Fibroepithelial lesions (FL) of the breast, in particular, phyllodes tumors (PT) 
      and fibroadenomas, pose a significant diagnostic challenge. There are no 
      generally accepted criteria that distinguish benign, borderline, malignant PT and 
      fibroadenomas. Combined genome-wide DNA methylation and copy number variant (CNV) 
      profiling is an emerging strategy to classify tumors. We compiled a series of 
      patient-derived archival biopsy specimens reflecting the FL spectrum and 
      histological mimickers including clinical follow-up data. DNA methylation and 
      CNVs were determined by well-established microarrays. Comparison of the patterns 
      with a pan-cancer dataset assembled from public resources including "The Cancer 
      Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) suggests that FLs form a 
      methylation class distinct from both control breast tissue as well as common 
      breast cancers. Complex CNVs were enriched in clinically aggressive FLs. 
      Subsequent fluorescence in situ hybridization (FISH) analysis detected respective 
      aberrations in the neoplastic mesenchymal component of FLs only, confirming that 
      the epithelial component is non-neoplastic. Of note, our approach could lead to 
      the elimination of the diagnostically problematic category of borderline PT and 
      allow for optimized prognostic patient stratification. Furthermore, the 
      identified recurrent genomic aberrations such as 1q gains (including MDM4), 
      CDKN2a/b deletions, and EGFR amplifications may inform therapeutic 
      decision-making.
FAU - Hench, Juergen
AU  - Hench J
AD  - Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 
      Basel, Switzerland.
FAU - Vlajnic, Tatjana
AU  - Vlajnic T
AUID- ORCID: 0000-0002-1067-6771
AD  - Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 
      Basel, Switzerland.
FAU - Soysal, Savas Deniz
AU  - Soysal SD
AUID- ORCID: 0000-0001-6165-0187
AD  - Visceral Surgery Research Laboratory, Clarunis, Department of Biomedicine, 
      University of Basel, 4031 Basel, Switzerland.
AD  - Department of Surgery, Clarunis University Center for Gastrointestinal and Liver 
      Diseases Basel, 4031 Basel, Switzerland.
FAU - Obermann, Ellen C
AU  - Obermann EC
AD  - Institute of Pathology, Cantonal Hospital Lucerne, 6000 Lucerne, Switzerland.
FAU - Frank, Stephan
AU  - Frank S
AD  - Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 
      Basel, Switzerland.
FAU - Muenst, Simone
AU  - Muenst S
AD  - Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 
      Basel, Switzerland.
LA  - eng
GR  - NA/Domarena Foundation/
GR  - NA/Parrotia Foundation/
PT  - Journal Article
DEP - 20220128
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8833410
OTO - NOTNLM
OT  - copy number alterations
OT  - dimension reduction
OT  - fibroepithelial breast lesions
OT  - methylation analysis
OT  - phyllodes tumors
OT  - unsupervised machine learning
COIS- S.M. is part of a digital advisory board for Roche. The other authors declare no 
      conflict of interest. The funders had no role in the design of the study; in the 
      collection, analyses, or interpretation of data; in the writing of the 
      manuscript, or in the decision to publish the results.
EDAT- 2022/02/16 06:00
MHDA- 2022/02/16 06:01
PMCR- 2022/01/28
CRDT- 2022/02/15 01:03
PHST- 2022/01/14 00:00 [received]
PHST- 2022/01/24 00:00 [revised]
PHST- 2022/01/26 00:00 [accepted]
PHST- 2022/02/15 01:03 [entrez]
PHST- 2022/02/16 06:00 [pubmed]
PHST- 2022/02/16 06:01 [medline]
PHST- 2022/01/28 00:00 [pmc-release]
AID - cancers14030667 [pii]
AID - cancers-14-00667 [pii]
AID - 10.3390/cancers14030667 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Jan 28;14(3):667. doi: 10.3390/cancers14030667.