PMID- 33382535
OWN - NLM
STAT- MEDLINE
DCOM- 20220126
LR  - 20240229
IS  - 2056-4538 (Electronic)
IS  - 2056-4538 (Linking)
VI  - 7
IP  - 3
DP  - 2021 May
TI  - Chromosome 2q gain and epigenetic silencing of GATA3 in microglandular adenosis 
      of the breast.
PG  - 220-232
LID - 10.1002/cjp2.195 [doi]
AB  - Microglandular adenosis (MGA) represents a rare neoplasm of the mammary gland, 
      which in a subset of cases may be associated with triple-negative breast cancer 
      (BC). The biology of MGA is poorly understood. In this study, eight MGA cases 
      (n = 4 with and n = 4 without associated BC) were subjected to a comprehensive 
      characterization using immunohistochemistry, genome-wide DNA copy number (CN) 
      profiling, fluorescence in situ hybridization (FISH), next-generation sequencing 
      (NGS), and DNA methylation profiling using 850 K arrays and bisulfite 
      pyrosequencing. Median patient age was 61 years (range 57-76 years). MGA lesions 
      were estrogen receptor (ER)-negative, progesterone receptor-negative, 
      HER2-negative, and S100-positive. DNA CN alterations (CNAs) were complex or 
      limited to few gains and losses. CN gain on chromosome 2q was the most common CNA 
      and was validated by FISH in five of eight cases. NGS demonstrated an average of 
      two mutations per case (range 0-5) affecting 10 different genes (ARID1A, ATM, 
      CTNNB1, FBXW7, FGFR2, MET, PIK3CA, PMS2, PTEN, and TP53). CNAs and mutations were 
      similar in MGA and adjacent BC, indicating clonal relatedness. DNA methylation 
      profiling identified aberrant hypermethylation of CpG sites within GATA3, a key 
      transcription factor required for luminal differentiation. Immunohistochemistry 
      showed regular GATA3 protein expression in the normal mammary epithelium and in 
      ER-positive BC. Conversely, GATA3 was reduced or lost in all MGA cases tested 
      (8/8). In conclusion, MGA is characterized by common CN gain on chromosome 2q and 
      loss of GATA3. Epigenetic inactivation of GATA3 may provide a new clue to the 
      peculiar biology of this rare neoplasia.
CI  - (c) 2020 The Authors. The Journal of Pathology: Clinical Research published by The 
      Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.
FAU - Radner, Martin
AU  - Radner M
AUID- ORCID: 0000-0001-6913-8380
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - van Luttikhuizen, Jana Lisa
AU  - van Luttikhuizen JL
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Bartels, Stephan
AU  - Bartels S
AUID- ORCID: 0000-0002-8903-2345
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Bublitz, Janin
AU  - Bublitz J
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Grote, Isabel
AU  - Grote I
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Rieger, Luisa
AU  - Rieger L
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Christgen, Henriette
AU  - Christgen H
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Stark, Helge
AU  - Stark H
AUID- ORCID: 0000-0002-2668-8056
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Werlein, Christopher
AU  - Werlein C
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Lafos, Marcel
AU  - Lafos M
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Steinemann, Doris
AU  - Steinemann D
AD  - Department of Human Genetics, Hannover Medical School, Hannover, Germany.
FAU - Lehmann, Ulrich
AU  - Lehmann U
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Christgen, Matthias
AU  - Christgen M
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
FAU - Kreipe, Hans
AU  - Kreipe H
AD  - Institute of Pathology, Hannover Medical School, Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201231
PL  - England
TA  - J Pathol Clin Res
JT  - The journal of pathology. Clinical research
JID - 101658534
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (GATA3 Transcription Factor)
RN  - 0 (GATA3 protein, human)
SB  - IM
MH  - Aged
MH  - Biomarkers, Tumor/analysis/*genetics
MH  - *Chromosome Aberrations
MH  - *Chromosomes, Human, Pair 2
MH  - *DNA Methylation
MH  - Female
MH  - Fibrocystic Breast Disease/chemistry/*genetics/pathology
MH  - GATA3 Transcription Factor/*genetics
MH  - *Gene Silencing
MH  - Humans
MH  - Middle Aged
MH  - Molecular Diagnostic Techniques
MH  - Precancerous Conditions/*genetics/metabolism/pathology
MH  - Triple Negative Breast Neoplasms/chemistry/*genetics/pathology
PMC - PMC8073017
OTO - NOTNLM
OT  - DNA methylation
OT  - breast cancer precursor
OT  - epigenetic alteration
OT  - luminal differentiation
OT  - stem cell
OT  - triple-negative breast cancer
EDAT- 2021/01/01 06:00
MHDA- 2022/01/27 06:00
PMCR- 2020/12/31
CRDT- 2020/12/31 12:10
PHST- 2020/11/06 00:00 [revised]
PHST- 2020/08/31 00:00 [received]
PHST- 2020/11/20 00:00 [accepted]
PHST- 2021/01/01 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2020/12/31 12:10 [entrez]
PHST- 2020/12/31 00:00 [pmc-release]
AID - CJP2195 [pii]
AID - 10.1002/cjp2.195 [doi]
PST - ppublish
SO  - J Pathol Clin Res. 2021 May;7(3):220-232. doi: 10.1002/cjp2.195. Epub 2020 Dec 
      31.