PIK3CA Mutations are Common in Many Tumor Types and are Often Associated With Other Driver Mutations.

OBJECTIVES

Genotyping clinical cancer specimens determines a fuller spectrum of mutations that an individual tumor harbors, and thus provides better insight into its molecular pathogenesis. Using genotyping data collected during routine clinical care our objective was to better determine the genomic landscape associated with PIK3CA mutations since much interest has been placed on PIK3CA targeted therapy.

METHODS

We performed multiplexed tumor genotyping within our CLIA-certified clinical laboratory on all consenting cancer patients who presented to the Brigham and Women's Hospital/Dana-Farber Cancer Center, regardless of histologic subtype. A total of 3252 cancers were genotyped for 471 mutations in 41 cancer-associated genes (including 23 mutations in PIK3CA), using a PCR-mass spectrometry assay.

RESULTS

A total of 288 (9%) samples contained a mutation in PIK3CA, involving 25 different primary sites. In 117 (41%) cases, the PIK3CA mutation was found with at least 1 other mutation, many known oncogenic drivers, while only 7% of the non-PIK3CA mutated cases, when comparing like tumor types, had >1 mutation (P<0.0001). Breast cancers had the highest rate of PIK3CA mutations (34%), which correlated with estrogen receptor + status (P=0.0002).

CONCLUSIONS

These findings suggest that PIK3CA mutations may be a relatively late event and may function primarily in a supporting/modifying role, and not as a primary driver of oncogenesis. Although further studies are needed, our observations during clinical tumor genotyping suggest that when other pro-oncogenic pathways are mutated along with PIK3CA, then, PIK3CA inhibition alone may not be effective and combination therapy may be warranted.