UNASSIGNED: @entity5 developed either as independent @entity5 or as intrahepatic metastases, are very common in primary @entity96 . However, their molecular pathogenesis remains elusive. Herein, a @entity1 with @entity157 ( @entity157 , designated as @entity157 -A and @entity157 -B) and one @entity1419 ( @entity1419 ), as well as two postoperative recurrent @entity5 , was enrolled. Multiregional whole-exome sequencing was applied to these @entity5 to delineate the clonality and heterogeneity. The three primary @entity5 showed almost no overlaps in mutations and copy number variations. Within each @entity5 , multiregional sequencing data showed varied intratumoral heterogeneity (21.6% in @entity157 -A, 20.4% in @entity157 -B, 53.2% in @entity1419 ). The mutational profile of two recurrent @entity5 showed obvious similarity with @entity157 -A (86.7% and 86.6% respectively), rather than others, indicating that they originated from @entity157 -A. The evolutionary history of the two recurrent @entity5 indicated that intrahepatic micro- @entity3 could be an early event during @entity157 progression. Notably, @entity70215 was the only gene mutated in two primary HCCs and the recurrences. Mutation prevalence screen and functional experiments showed that @entity70215 , harboring somatic coding mutations in 26.7% of @entity157 , could potently inhibit growth and invasion of @entity157 cells. In @entity157 @entity1 , both @entity70215 expression and @entity70215 mutational status significantly correlated with @entity1 prognosis. Together, our findings suggest that spatial and temporal dissection of genomic alterations during the progression of multifocal @entity96 may help to elucidate the basis for its dismal prognosis. @entity70215 acts as a putative @entity5 suppressor that is frequently inactivated in @entity1 @entity157 .

Inferring the progression of multifocal XXXX from spatial and temporal genomic heterogeneity.

@entity1 :: ('9606', 'Species') :: ['patients', 'human', 'patient'] @entity96 :: ('MESH:D008113', 'Disease') :: ['liver cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'Multifocal tumors'] @entity70215 :: ('79633', 'Gene') :: ['FAT4'] @entity1419 :: ('MESH:C535533', 'Disease') :: ['ICC', 'intrahepatic cholangiocarcinoma'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis'] @entity157 :: ('MESH:D006528', 'Disease') :: ['HCC', 'synchronous two hepatocellular carcinoma']
@entity96 :: (MESH:D008113,Disease) :: ['liver cancer']
