Altered Lamin A/C splice variant expression as a possible diagnostic marker in breast cancer

Abstract

Background: Lamin A/C alternative splice variants (Lamin A, Lamin C, Lamin AΔ10 and Lamin AΔ50) have been implicated in cell cycle regulation, DNA replication, transcription regulation, cellular differentiation, apoptosis and aging. In addition, loss of Lamin A/C expression has been observed in several cancers, including breast cancer, and it has been found that Lamin A/C suppression may lead to cancer-like aberrations in nuclear morphology and aneuploidy. Based on these observations, we hypothesized that Lamin A/C transcript variant quantification might be employed for the diagnosis of breast cancer.

Methods: Newly designed TaqMan qRT-PCR assays for the analysis of Lamin A/C splice variants were validated and their use as biomarkers for the diagnosis of breast cancer was assessed using 16 normal breast tissues and 128 breast adenocarcinomas. In addition, the expression levels of the Lamin A/C transcript variants were measured in samples derived from seven other types of cancer.

Results: We found that the expression level of Lamin C was significantly increased in the breast tumors tested, whereas the expression levels of Lamin A and Lamin AΔ50 were significantly decreased. No significant change in Lamin AΔ10 expression was observed. Our data also indicated that the Lamin C : Lamin A mRNA ratio was increased in all clinical stages of breast cancer. Additionally, we observed increased Lamin C : Lamin A mRNA ratios in liver, lung and thyroid carcinomas and in colon, ovary and prostate adenocarcinomas.

Conclusions: From our data we conclude that the Lamin C : Lamin A mRNA ratio is increased in breast cancer and that this mRNA ratio may be of diagnostic use in all clinical stages of breast cancer and, possibly, also in liver, lung, thyroid, colon, ovary and prostate cancers.

Keywords: Breast cancer; Lamin A/C; Metastasis; Progerin; Tumor marker.