TMSB4Y is a candidate tumor suppressor on the Y chromosome and is deleted in male breast cancer.

Hong Yuen Wong,Julia A Beaver,Anita Aggarwal,Sarah Croessmann,David Chu,Daniel J Zabransky,Pedram Argani,Josh Lauring,Min-Ling Liu,Justin Cidado,Ben Ho Park,Rory L Cochran,Joseph P Garay,Paula J Hurley,Grace M Wang,Alan Meeker

doi:10.18632/oncotarget.6743

Hong Yuen Wong, Julia A Beaver + Show 14 more

Open Access

https://doi.org/10.18632/oncotarget.6743

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Abstract

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 β-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.

Highlights

To address the hypothesis that Y chromosome loss may have a role in breast carcinogenesis, we first evaluated its loss in male breast cancers
In order to analyze the remaining 3 samples that were unevaluable by fluorescence in situ hybridization (FISH), we performed droplet digital PCR (ddPCR) on Formalin fixed paraffin embedded (FFPE) DNA using Taqman probes and primers specific to the X and Y chromosomes to assay for Y chromosome loss
Cancer is a disease caused by a successive series of genetic alterations that lead to selective proliferative advantages in a single cell, which expands into a tumorigenic clone [33]

Summary

Introduction

Male breast cancer is a rare disease that is 100-fold less common than female breast cancer and accounts for less than 1% of all cancers in men [1, 2]. Male breast cancer has an annual average incidence of

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Conclusion