Homozygous deletion of SMAD4 in breast cancer cell lines and invasive ductal carcinomas

Cancer Biology & Therapy
Diansheng ZhongWei Zhou

Abstract

Inactivation of TGF-beta/SMAD4 signaling was postulated to play an important role in breast cancer development. Even though SMAD4 is located on 18q21, a region frequently lost in breast cancers, point mutations of SMAD4 were rarely observed, implying that biallelic inactivation of SMAD4 was not necessary in the process. In this study, a novel homozygous deletion of SMAD4 was identified in breast cancer cell line SW527 during a screening of 31 breast cancer cell lines. As several breast cancer cell lines were shown to contain SMAD4 homozygous deletion, we sought to develop a reliable method to access such lesions in archived primary tumor specimens. First, a DNA quantification method was developed to measure as few as 5 copies of DNA templates so that the amount of genomic DNA isolated by laser-capture microdissection can be accurately determined. Next, accurate DNA quantitation allowed sufficient DNA templates to be included in the homozygous deletion assay for the robust amplification of SMAD4 genetic markers. Two out of 24 primary infiltrative ductal carcinomas (IDC) with 18q allelic imbalance were determined to contain SMAD4 homozygous deletions, and these samples are also negative for Smad4 protein expression by immunohisto...Continue Reading

Citations

Jan 21, 2010·International Journal of Biological Sciences·Guan Yang, Xiao Yang
Feb 11, 2012·FEBS Letters·Stephen P Malkoski, Xiao-Jing Wang
Dec 2, 2015·Oncology Letters·Nannan LiuYuhe Liu
Nov 5, 2008·Cancer Letters·Emma-Leena AlarmoAnne Kallioniemi
Mar 15, 2015·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Kaisheng MaoWei Zhou
Dec 24, 2019·Frontiers in Oncology·Li-Han LinChung-Ji Liu

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