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SUMMARY:Exon Array Analysis of Head and Neck Cancers Identifies a Hypoxia 
 Related Splice Variant of LAMA3 Associated with a Poor Prognosis - Xin Wan
 g
DTSTART:20100308T153000Z
DTEND:20100308T163000Z
UID:TALK23270@talks.cam.ac.uk
CONTACT:Stefan Gräf
DESCRIPTION:The identification of alternatively spliced transcript variant
 s specific to particular biological processes in tumours should increase o
 ur understanding of cancer. Hypoxia is an important factor in cancer biolo
 gy\, and associated splice variants may present new markers to help with p
 lanning treatment. A method was developed to analyse alternative splicing 
 in exon array data\, using probeset multiplicity to identify genes with ch
 anges in expression across their loci\, and a combination of the splicing 
 index and a new metric based on the variation of reliability weighted fold
  changes to detect changes in the splicing patterns. The approach was vali
 dated on a cancer/normal sample dataset in which alternative splicing even
 ts had been confirmed using RT-PCR. We then analysed ten head and neck squ
 amous cell carcinomas using exon arrays and identified differentially expr
 essed splice variants in five samples with high versus five with low level
 s of hypoxia-associated genes. The analysis identified a splice variant of
  LAMA3 (Laminin α 3)\, LAMA3-A\, known to be involved in tumour cell inva
 sion and progression. The full-length transcript of the gene (LAMA3-B) did
  not appear to be hypoxia-associated. The results were confirmed using qua
 litative RT-PCR. In a series of 59 prospectively collected head and neck t
 umours\, expression of LAMA3-A had prognostic significance whereas LAMA3-B
  did not. This work illustrates the potential for alternatively spliced tr
 anscripts to act as biomarkers of disease prognosis with improved specific
 ity for particular tissues or conditions over assays which do not discrimi
 nate between splice variants.
LOCATION:Room 132\, CRI
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