Novel SNP improves differential survivability and mortality in non-small cell lung cancer patients — ASN Events

Novel SNP improves differential survivability and mortality in non-small cell lung cancer patients (#60)

Tzia Liang Mah 1 , Xin Ning Adeline Yap 1 , Vachiranee Limviphuvadh 2 , Nanpu Li 1 , Srinath Sridharan 1 , Vellaisemy Kuralmani 1 , Mengling Feng 1 , Natalia Liem 3 , Sharmila Adhikari 2 , Wei Peng Yong 3 , Ross A Soo 3 , Sebastian Maurer-Stroh 2 , Frank Eisenhaber 2 , Joo Chuan Tong 4
  1. Institute for Infocomm Research, Singapore
  2. Bioinformatics Institute, Singapore
  3. National University Health System, Singapore
  4. Institute of High Performance Computing, Singapore

Background: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide due to poor patient prognosis and clinical outcome. Here, we studied the genetic variations underlying NSCLC pathogenesis based on their association to patient outcome after gemcitabine therapy.

Methods: Bioinformatics analysis was used to investigate possible effects of POLA2 G583R (POLA2+1747=GG/GA, dbSNP ID: rs487989) in terms of protein function. Using biostatistics, POLA2+1747=GG/GA (rs487989, POLA2 G583R) was identified as strongly associated with mortality rate and survival time among NSCLC patients.

Results: It was also shown that POLA2+1747=GG/GA is functionally significant for protein localization via green fluorescent protein (GFP)-tagging and confocal laser scanning microscopy analysis. The single nucleotide polymorphism (SNP) causes DNA polymerase alpha subunit B to localize in the cytoplasm instead of the nucleus. This inhibits DNA replication in cancer cells and confers a protective effect in individuals with this SNP.

Conclusions: The results suggest that POLA2+1747=GG/GAmay be used as a prognostic biomarker of patient outcome in NSCLC pathogenesis.