INST 1204: PIK3CA Mutations as Biomarkers for Metastasis in Colon Cancer

Primary outcomes

1. The best standardized method for high throughput DNA extraction and analysis from colon tumors of patients

   Time frame: Through study completion, up to 20 years

   Develop and standardize methods for high throughput DNA extraction and analysis from colon tumors of patients with stage II and stage Ill disease harboring PIK3CA exon 9 and exon 20 mutations.

   Currently, commercially available kits to assay for the Pl3K mutations rely on Sanger sequencing of DNA products extracted from formalin fixed paraffin embedded (FFPE) tissues. The presence of a pseudogene on chromosome 22 can interfere with the detection of helical domain mutations. A pyrosequencing technique which allows one to "sequence by synthesis" has been developed to allow the detection of the hotspot PIK3CA mutations without interference from this pseudogene. The investigators propose to modify and expand this pyrosequencing technique to include the additional mutations identified in exons 9 and 20, allowing identifications of nearly 85% of all PIK3CA mutations. Prior to sequencing the investigators will op

2. The correlation between wild type PIK3CA, PIK3CA exon 9 and PIK3CA exon 20 mutations and developing of metastatic disease and overall colorectal patient survival

   Time frame: Through study completion, up to 20 years

   Tissues from stage II and stage Ill colorectal cancer patients have been identified in the University of New Mexico (UNM) Human Tissue Repository (HTR) and will be available for analysis. Clinical follow up data including the development of metastases, site(s) of metastases and overall survival will be collected from a combination of the tumor registry and the medical records. Additional formalin fixed paraffin embedded tissues from patients with stage II and Ill colorectal cancer will be available from the NCI Prostate, Lung, Colon, Ovary Prevention Trial. Extensive clinical follow-up and survival data are already annotated for patients in this trial and will be available for analysis. Correlation between wild type PIK3CA, exon 9 and exon 20 PIK3CA mutants, KRAS and BRAF mutational status and the occurrence of metastases will be determined. Survival curves will also be generated based on mutational status of the genes listed above.