PMID- 26702755
OWN - NLM
STAT- MEDLINE
DCOM- 20161107
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 42
DP  - 2015 Dec 29
TI  - TMSB4Y is a candidate tumor suppressor on the Y chromosome and is deleted in male 
      breast cancer.
PG  - 44927-40
LID - 10.18632/oncotarget.6743 [doi]
AB  - Male breast cancer comprises less than 1% of breast cancer diagnoses. Although 
      estrogen exposure has been causally linked to the development of female breast 
      cancers, the etiology of male breast cancer is unclear. Here, we show via 
      fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that 
      the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two 
      independent cohorts of male breast cancer patients. We also show somatic loss of 
      the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of 
      loss at this locus in male breast cancers. To further understand the function of 
      TMSB4Y, we created inducible cell lines of TMSB4Y in the female human breast 
      epithelial cell line MCF-10A. Expression of TMSB4Y resulted in aberrant cellular 
      morphology and reduced cell proliferation, with a corresponding reduction in the 
      fraction of metaphase cells. We further show that TMSB4Y interacts directly with 
      beta-actin, the main component of the actin cytoskeleton and a cell cycle modulator. 
      Taken together, our results suggest that clonal loss of the Y chromosome may 
      contribute to male breast carcinogenesis, and that the TMSB4Y gene has tumor 
      suppressor properties.
FAU - Wong, Hong Yuen
AU  - Wong HY
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Wang, Grace M
AU  - Wang GM
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Croessmann, Sarah
AU  - Croessmann S
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Zabransky, Daniel J
AU  - Zabransky DJ
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Chu, David
AU  - Chu D
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Garay, Joseph P
AU  - Garay JP
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Cidado, Justin
AU  - Cidado J
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
AD  - Present address: Oncology iMED, AstraZeneca, Waltham, MA, USA.
FAU - Cochran, Rory L
AU  - Cochran RL
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Beaver, Julia A
AU  - Beaver JA
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Aggarwal, Anita
AU  - Aggarwal A
AD  - Veterans Affairs Medical Center, Washington, DC, USA.
AD  - The Georgetown University, Washington, DC, USA.
AD  - George Washington University School of Medicine, Washington, DC, USA.
FAU - Liu, Min-Ling
AU  - Liu ML
AD  - Veterans Affairs Medical Center, Washington, DC, USA.
AD  - George Washington University School of Medicine, Washington, DC, USA.
FAU - Argani, Pedram
AU  - Argani P
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Meeker, Alan
AU  - Meeker A
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Hurley, Paula J
AU  - Hurley PJ
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Lauring, Josh
AU  - Lauring J
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Park, Ben Ho
AU  - Park BH
AD  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
AD  - The Whiting School of Engineering, Department of Chemical and Biomolecular 
      Engineering, The Johns Hopkins University, Baltimore, MD, USA.
LA  - eng
GR  - CA167939/CA/NCI NIH HHS/United States
GR  - T32 GM007309/GM/NIGMS NIH HHS/United States
GR  - P30 CA006973/CA/NCI NIH HHS/United States
GR  - T32 CA106183/CA/NCI NIH HHS/United States
GR  - NIH GM007309/GM/NIGMS NIH HHS/United States
GR  - F31 CA167939/CA/NCI NIH HHS/United States
GR  - CA168180/CA/NCI NIH HHS/United States
GR  - NIH P30 CA006973/CA/NCI NIH HHS/United States
GR  - T32 GM008752/GM/NIGMS NIH HHS/United States
GR  - F31 CA168180/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Actins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 549LM7U24W (thymosin beta(4))
RN  - 61512-21-8 (Thymosin)
SB  - IM
MH  - Actins/genetics/metabolism
MH  - Breast Neoplasms, Male/*genetics/metabolism/pathology
MH  - Cell Line
MH  - Cell Proliferation
MH  - Cell Shape
MH  - Cell Transformation, Neoplastic/genetics/metabolism/pathology
MH  - *Chromosomes, Human, Y
MH  - Female
MH  - *Gene Deletion
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mammary Glands, Human/metabolism/pathology
MH  - Phenotype
MH  - Polymerase Chain Reaction
MH  - Thymosin/*genetics/metabolism
MH  - Time Factors
MH  - Transfection
MH  - Tumor Suppressor Proteins/*genetics/metabolism
PMC - PMC4792601
OTO - NOTNLM
OT  - TMSB4Y
OT  - Y chromosome
OT  - cancer genetics
OT  - male breast cancer
OT  - tumor suppressor
COIS- CONFLICTS OF INTEREST B.H.P. is a paid member of scientific advisory boards for 
      Horizon Discovery, LTD and Loxo Oncology, and has research contracts with Genomic 
      Health, Inc and Foundation Medicine. Under separate licensing agreements between 
      Horizon Discovery, LTD and The Johns Hopkins University, B.H.P. is entitled to a 
      share of royalties received by the University on sales of products. The terms of 
      this arrangement are being managed by the Johns Hopkins University, in accordance 
      with its conflict of interest policies. No potential conflicts of interest were 
      disclosed by the other authors.
EDAT- 2015/12/26 06:00
MHDA- 2016/11/08 06:00
PMCR- 2015/12/29
CRDT- 2015/12/26 06:00
PHST- 2015/11/30 00:00 [received]
PHST- 2015/12/20 00:00 [accepted]
PHST- 2015/12/26 06:00 [entrez]
PHST- 2015/12/26 06:00 [pubmed]
PHST- 2016/11/08 06:00 [medline]
PHST- 2015/12/29 00:00 [pmc-release]
AID - 6743 [pii]
AID - 10.18632/oncotarget.6743 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Dec 29;6(42):44927-40. doi: 10.18632/oncotarget.6743.