Co-Evolution of Somatic Variation in Primary and Metastatic XXXX May Expand Biopsy Indications in the Molecular Era.

@entity1 @entity33700 @entity17731 @entity7379 @entity5 @entity984 @entity2536 @entity10484 @entity71330 @entity876 @entity6295 @entity26562 @entity14 @entity3 @entity1594 @entity71535
INTRODUCTION: @entity3 is thought to be a clonal event whereby a single cell initiates the development of a new @entity5 at a distant site. However the degree to which primary and @entity3 differ on a molecular level remains unclear. To further evaluate these concepts, we used next generation sequencing (NGS) to assess the molecular composition of paired primary and metastatic @entity14 tissue specimens. METHODS: 468 @entity14 samples from a large personalized medicine initiative were assessed by targeted gene sequencing of 1,321 individual genes. Eighteen @entity1 produced genomic profiles for 17 paired primary:metastatic (and 2 metastatic:metastatic) specimens. RESULTS: An average of 33.3 mutations/ @entity5 were concordant (shared) between matched samples, including common well-known genes ( @entity6295 , @entity984 , @entity876 ). An average of 2.3 mutations/ @entity5 were discordant (unshared) among paired sites. @entity984 mutational status was always concordant. The overall concordance rate for mutations was 93.5%; however, nearly all (18/19 (94.7%)) paired @entity5 showed at least one mutational discordance. Mutations were seen in: @entity10484 , the largest gene (5 discordant pairs), @entity71330 , @entity6295 , @entity71535 , @entity33700 , @entity876 , and @entity17731 (2 discordant pairs), @entity2536 , @entity7379 , @entity1594 , @entity26562 , and 66 others (1 discordant pair). CONCLUSIONS: Whereas primary and @entity3 displayed little variance overall, co-evolution produced incremental mutations in both. These results suggest that while biopsy of the @entity5 alone is likely sufficient in the chemotherapy-na  ve @entity1 , additional biopsies of primary or metastatic disease may be necessary to precisely tailor therapy following chemotherapy resistance or insensitivity in order to adequately account for @entity5 evolution.
