Affiliations: Cancer Genetics Lab, Department of Biosciences,
COMSATS Institute of Information Technology, Chak shazad, Islamabad,
Pakistan | Metastasis and Angiogenesis Research Group, Institute
of Cancer and Genetics, Cardiff University School of Medicine, Cardiff,
UK
Note: [] Corresponding author: Ruqia Mehmood Baig, Cancer Genetics Lab,
Department of Biosciences, COMSATS Institute of Information Technology, Park
Road, Chak shazad, Islamabad, Pakistan. Tel.: +92 313 5400921; Fax: +92 51
9247006; E-mail: [email protected]
Abstract: Cytoskeletal rearrangement occurs in variety of cellular processes
and involves a wide spectrum of proteins. Gelsolin super family proteins
control actin organization by severing and capping filament ends and nucleating
actin assembly. Gelsolin is the founding member of this family and plays
important role in pathogenesis of human neoplasia. This study aimed to investigate the germline mutations and
expressional profile of Gelsolin in human breast cancer tissues. For germ line
screening PCR-SSCP technique was used while expression was analyzed through
quantitative real time PCR. Different types of mutations were observed in
Gelsolin coding regions on exons 4, 10, 11, 14 and 15. These mutations include
3 missense nonsynonymous substitution mutations, 2 deletions, 1 insertion and 1
synonymous substitution mutation. Gelsolin transcript level was found
significantly lower in breast tumor tissues compared to control samples
(p=0.03). Low level of Gelsolin was found in metastatic patients (p=0.002) and
patients who died from breast cancer (P=0.03) compared to disease free patients
at final follow up. This study shows that level of Gelsolin is down regulated
in breast cancer tissues and is linked with metastasis development and death in
patients. It is concluded that genetic changes in coding regions of Gelsolin
can potentially contribute to genetic instability. These genetic variations and
expressional correlation with patient survival may prove to be of significant
importance.
Keywords: Gelsolin, germline mutations, PCR-SSCP, expressional analysis, quantitative real time PCR, breast cancer
