title: Mutational spectrum of Gelsolin and its down regulation is associated with breast cancer.
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.
authors: Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Chak shazad, Islamabad, Pakistan. ruqiamehmood@gmail.com
authors: Ruqia Mehmood
authors: RM
authors: Baig
authors: Ishrat
authors: I
authors: Mahjabeen
authors: Maimoona
authors: M
authors: Sabir
authors: Nosheen
authors: N
authors: Masood
authors: Kashif
authors: K
authors: Ali
authors: Faraz Arshad
authors: FA
authors: Malik
authors: Mahmood Akhtar
authors: MA
authors: Kayani
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D016368:Frameshift Mutation; D018260:Gelsolin / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010154:Pakistan; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D018260:Gelsolin