Road map for fibrolamellar carcinoma: progress and goals of a diversified approach

Figures & data

Table 1 Key recent developments

Finding	References
A crystal structure of the fusion protein retains a kinase domain structure and binding sites to anchorage and regulatory proteins similar to wild-type PRKACA	^Citation1
Some FLCs can be grown and propagated in immunocompromised mice and can maintain many key characteristics	^Citation2
DNAJB1-PRKACA is functionally confirmed to drive tumorigenesis in mice, further supported by Wnt pathway signaling and fibrosis	^Citation3, ^Citation4
The DNAJB1-PRKACA fusion oncogene is specific for FLC. It has not been observed in any of the tens of thousands of cancer genomes sequenced from nonliver tumors in TCGA or MSK-IMPACT™ studies	^Citation5, ^Citation6
Interaction of AKAP anchorage proteins and the PKA holoenzyme regulates PKA signaling without requiring dissociation of catalytic and regulatory subunits	^Citation7

Abbreviations: FLC, fibrolamellar carcinoma; PKA, protein kinase A; TCGA, The Cancer Genome Atlas.

Figure 1 The Second Fibrolamellar Cancer Foundation Scientific Summit developed a “road map” for a collaborative, multidisciplinary approach to improve outcomes for patients with fibrolamellar carcinoma.

CheungJGinterCCassidyMStructural insights into misregulation of protein kinase A in human tumorsProc Natl Acad Sci U S A201511251374137925605907

 PubMed Web of Science ®Google Scholar

OikawaTWauthierEDinhTAModel of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cellsNat Commun201561807026437858

 PubMed Web of Science ®Google Scholar

EngelholmLHRiazASerraDCRISPR/Cas9 engineering of adult mouse liver demonstrates that the dnajb1-prkaca gene fusion is sufficient to induce tumors resembling fibrolamellar hepatocellular carcinomaGastroenterology201715361662167328923495

 PubMed Web of Science ®Google Scholar

KastenhuberERLalazarGHoulihanSLDNAJB1-PRKACA fusion kinase interacts with β-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinomaProc Natl Acad Sci U S A201711450130761308429162699

 PubMed Web of Science ®Google Scholar

DinhTAVitucciECWauthierEComprehensive analysis of the Cancer genome atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinomaSci Rep2017714465328304380

 PubMed Web of Science ®Google Scholar

ZehirABenayedRShahRHMutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patientsNat Med201723670371328481359

 PubMed Web of Science ®Google Scholar

SmithFDEsseltineJLNygrenPJLocal protein kinase a action proceeds through intact holoenzymesScience201735663441288129328642438

 PubMed Web of Science ®Google Scholar