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Fibrolamellar hepatocellular carcinoma

August 22, 2023

Fibrolamellar carcinoma (FLC) is a rare form of carcinoma that typically affects young adults and is characterized, under the microscope, by laminated fibrous layers interspersed between the tumor cells.[1] It has been estimated that 200 new cases are diagnosed worldwide each year.[2] However, in light of recent advances in our molecular understanding, this has recently been revised to suggest it may be at least ten times more common.[3] FLC, also known as fibrolamellar hepatocellular carcinoma, is different from the more common hepatocellular carcinoma (HCC) in that it afflicts young people with normal liver function and no known risk factors.[1][2][4][5]

Fibrolamellar hepatocellular carcinoma
Other namesFHCC
Micrograph of fibrolamellar hepatocarcinoma showing the characteristic laminated fibrosis between the tumor cells with a low NC ratio. H&E stain.
SpecialtyOncology 

Cause

A 2014 study showed the presence of the DNAJB1-PRKACA chimeric transcript (resulting from a 400kb somatic deletion on chromosome 19) in 100% of the FLCs examined (15/15).[6][7] This gene fusion has been confirmed in many other studies.[8][9][10] That this genomic deletion is sufficient to produce FLC was shown by creating this deletion, and formation of the DNAJB1::PRKACA chimeric gene, using CRISPR/Cas9 in the livers of mice.[11][12] That the actual formation of the DNAJB1::PRKACA was responsible, and not the deletion, was shown by expression of the DNAJB1::PRKACA from a transposon.[11] To determine if the DNAJB1::PRKACA was only involved in triggering the tumor, or if it continued to drive the tumor, a small hairpin RNA was used to eliminate the DNAJB1::PRKACA. The tumors died, which demonstrated not only that DNAJB1::PRKACA is continuing to drive FLC, but that the tumor has become oncogenically addicted.[13]

Pathology

The histopathology of FLC is characterized by laminated fibrous layers, interspersed between the tumor cells. Cytologically, the tumor cells have a low nuclear to cytoplasmic ratio with abundant eosinophilic cytoplasm.[1] Tumors are non-encapsulated, but well circumscribed, when compared to conventional HCC (which typically has an invasive border).[citation needed]

Diagnosis

Due to lack of symptoms, until the tumor is sizable, this form of cancer is often advanced when diagnosed. Symptoms include vague abdominal pain, nausea, abdominal fullness, malaise and weight loss. They may also include a palpable liver mass.[14] Other presentations include jaundice, ascites, fulminant liver failure, encephalopathy, gynecomastia (males only), thrombophlebitis of the lower limbs, recurrent deep vein thrombosis, anemia and hypoglycemia.[citation needed]

The usual markers for liver disease – aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase – are often normal or only slightly elevated. FLC often does not produce alpha fetoprotein (AFP), a widely used marker for conventional hepatocellular carcinoma. In a subset of FLC patients elevated plasma neurotensin levels may be present.[15] Likewise, in a subset of FLC patients, elevated serum vitamin B12 binding globulin levels may be present.[16]

Diagnosis is normally made by imaging (ultrasound, CT or MRI) and biopsy.[17] However, even with a biopsy, there is often disagreement over the diagnosis.[17] Since the characterization of the DNAJB1::PRKACA fusion, the most reliable diagnosis is through molecular characterization such as PCR to detect the fusion,[7][18] or genomic sequencing, or using a fluorescent in-situ hybridization.[8]

Treatment

FLC can often be surgically removed. Liver resection is the optimal treatment and may need to be performed more than once, since this disease has a very high recurrence rate.[19] Due to such recurrence, periodic follow-up medical imaging (CT or MRI) is necessary.[19]

When the tumor cannot be removed surgically or when there is distant spread, many different systemic therapies are currently being used to treat the disease. However, no standard of care currently exists for FLC. Consequently, there remains a pressing need to identify proven, effective systemic therapies for the cancer. [2][20][21] Radiotherapy has been used but data is limited concerning its use.

The Fibrolamellar Registry, (http://fibroregistry.org)[22] a patient and family run medical registry has collected data from over 250 patients. This work has been used in multiple publications which include extended information on patient outcomes, efficacy of immune checkpoint inhibitors, efficacy of specific drugs and understanding the basis of high ammonia in FLC.[19][23][24][18]

The Fibroregistry[22] has answers to frequently asked questions (https://fibroregistry.org/faq-fibrolamellar/ ) as well as plain-language summaries of the science literature for understanding the success rate of some treatment approaches (https://fibroregistry.org/published-papers/ ). The FibroFoundation has resources available on different FLC treatment options. [25]

The survival rate for FLC largely depends on whether (and to what degree) the cancer has metastasized, i.e. spread to the lymph nodes or other organs. Distant spread (metastases), significantly reduces the median survival rate.[19] Five-year survival rates vary between 40–90%.[19]

Epidemiology

FLC accounts for 1–10% of primary liver cancers.[26] It typically has a young age at presentation when compared to conventional HCC. Previously it was estimated to be 20-40 years, mean ages 27 years,[27] but when analysis is restricted to those patients who are confirmed with a molecular test to have FLC, the age range is 10-40 and mean age of 21 years.[19] Unlike the more common HCC, patients most often do not have coexistent liver disease such as cirrhosis.

History

This disease was first described by Hugh Edmondson in a 14-year-old female with no underlying liver disease.[28] The name fibrolamellar hepatocellular carcinoma was coined by Craig et al. in 1980.[29] It was not recognized as a distinct form of cancer by the WHO until 2010.[30]

Starting in 2010, some patients and their family members started to examine the molecular basis of FLC.[20] They gathered samples through social media,[31][32] sequenced the genome, and analyzed the immunological response. Since there are few patients at any one institution, they formed their own medical registry, which allowed them to follow patients as they changed institutions (http://fibroregistry.org).[22] This work led to the identification of the chimeric fusion driver and the first characterization of the transcriptome and proteome. The work was heralded by Francis Collins when he presented to the Senate Appropriations committee[33] and was used by President Obama at the launch of The Precision Medicine Initiative at the White House.[34]

Additional images

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    Intermed. mag.

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    High mag.

References

  1. ^ a b c Torbenson, Michael (2012). "Fibrolamellar Carcinoma: 2012 Update". Scientifica. 2012: 1–15. doi:10.6064/2012/743790. PMC 3820672.
  2. ^ a b c O'Neill, Allison F.; Church, Alanna J.; Perez-Atayde, Antonio R.; Shaikh, Raja; Marcus, Karen J.; Vakili, Khashayar (August 2021). "Fibrolamellar carcinoma: An entity all its own". Current Problems in Cancer. 45 (4): 100770. doi:10.1016/j.currproblcancer.2021.100770.
  3. ^ Zack, Travis; Losert, Kurt P.; Maisel, Samantha M.; Wild, Jennifer; Yaqubie, Amin; Herman, Michael; Knox, Jennifer J.; Mayer, Robert J.; Venook, Alan P.; Butte, Atul; O’Neill, Allison F.; Abou-Alfa, Ghassan K.; Gordan, John D. (23 March 2023). "Defining incidence and complications of fibrolamellar liver cancer through tiered computational analysis of clinical data". npj Precision Oncology. 7 (1). doi:10.1038/s41698-023-00371-2.
  4. ^ Lalazar, Gadi; Simon, Sanford (February 2018). "Fibrolamellar Carcinoma: Recent Advances and Unresolved Questions on the Molecular Mechanisms". Seminars in Liver Disease. 38 (01): 051–059. doi:10.1055/s-0037-1621710. PMC 6020845.
  5. ^ "What is Fibrolamellar Carcinoma?". Fibrolamellar Cancer Foundation. Retrieved 2023-01-10.
  6. ^ "Teen Makes Genetic Discovery of Her Own Rare Cancer".
  7. ^ a b Honeyman JN, Simon EP, Robine N, Chiaroni-Clarke R, Darcy DG, Lim II, Gleason CE, Murphy JM, Rosenberg BR, Teegan L, Takacs CN, Botero S, Belote R, Germer S, Emde AK, Vacic V, Bhanot U, LaQuaglia MP, Simon SM (28 February 2014). "Detection of a Recurrent DNAJB1-PRKACA Chimeric Transcript in Fibrolamellar Hepatocellular Carcinoma". Science. 343 (6174): 1010–4. Bibcode:2014Sci...343.1010H. doi:10.1126/science.1249484. PMC 4286414. PMID 24578576.
  8. ^ a b Graham, Rondell P; Jin, Long; Knutson, Darlene L; Kloft-Nelson, Sara M; Greipp, Patricia T; Waldburger, Nina; Roessler, Stephanie; Longerich, Thomas; Roberts, Lewis R; Oliveira, Andre M; Halling, Kevin C; Schirmacher, Peter; Torbenson, Michael S (June 2015). "DNAJB1-PRKACA is specific for fibrolamellar carcinoma". Modern Pathology. 28 (6): 822–829. doi:10.1038/modpathol.2015.4.
  9. ^ Xu, Lei; Hazard, Florette K.; Zmoos, Anne-Flore; Jahchan, Nadine; Chaib, Hassan; Garfin, Phillip M.; Rangaswami, Arun; Snyder, Michael P.; Sage, Julien (1 January 2015). "Genomic analysis of fibrolamellar hepatocellular carcinoma". Human Molecular Genetics. 24 (1): 50–63. doi:10.1093/hmg/ddu418. PMC 4262492.
  10. ^ Dinh TA, Vitucci EC, Wauthier E, Graham RP, Pitman WA, Oikawa T, Chen M, Silva G, Greene KG, Torbenson MS, Reid LM, Sethupathy P (2017) Comprehensive analysis of The Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma. Sci Rep 7:44653. doi: 10.1038/srep44653
  11. ^ a b Kastenhuber, Edward R.; Lalazar, Gadi; Houlihan, Shauna L.; Tschaharganeh, Darjus F.; Baslan, Timour; Chen, Chi-Chao; Requena, David; Tian, Sha; Bosbach, Benedikt; Wilkinson, John E.; Simon, Sanford M.; Lowe, Scott W. (12 December 2017). "DNAJB1–PRKACA fusion kinase interacts with β-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma". Proceedings of the National Academy of Sciences. 114 (50): 13076–13084. doi:10.1073/pnas.1716483114. PMC 5740683.
  12. ^ Engelholm, Lars H.; Riaz, Anjum; Serra, Denise; Dagnæs-Hansen, Frederik; Johansen, Jens V.; Santoni-Rugiu, Eric; Hansen, Steen H.; Niola, Francesco; Frödin, Morten (December 2017). "CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1–Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma". Gastroenterology. 153 (6): 1662–1673.e10. doi:10.1053/j.gastro.2017.09.008.
  13. ^ Neumayer, Christoph; Ng, Denise; Jiang, Caroline S.; Qureshi, Adam; Lalazar, Gadi; Vaughan, Roger; Simon, Sanford M. (4 January 2023). "Oncogenic Addiction of Fibrolamellar Hepatocellular Carcinoma to the Fusion Kinase DNAJB1-PRKACA". Clinical Cancer Research. 29 (1): 271–278. doi:10.1158/1078-0432.CCR-22-1851. PMC 9811160.
  14. ^ Yen, JB.; Chang, KW. (2009). "Fibrolamellar hepatocellular carcinoma- report of a case". Chang Gung Med J. 32 (3): 336–9. PMID 19527614.
  15. ^ Collier, N.A.; Bloom, S.R.; Hodgson, H.J.F.; Weinbren, K.; Lee, Y.C.; Blumgart, L.H. (March 1984). "NEUROTENSIN SECRETION BY FIBROLAMELLAR CARCINOMA OF THE LIVER". The Lancet. 323 (8376): 538–540. doi:10.1016/s0140-6736(84)90934-6.
  16. ^ Paradinas, F J; Melia, W M; Wilkinson, M L; Portmann, B; Johnson, P J; Murray-Lyon, I M; Williams, R (25 September 1982). "High serum vitamin B12 binding capacity as a marker of the fibrolamellar variant of hepatocellular carcinoma". BMJ. 285 (6345): 840–842. doi:10.1136/bmj.285.6345.840. PMC 1499744.
  17. ^ a b Malouf, G; Falissard, B; Azoulay, D; Callea, F; Ferrell, L D; Goodman, Z D; Hayashi, Y; Hsu, H-C; Hubscher, S G; Kojiro, M; Ng, I O; Paterson, A C; Reynes, M; Zafrani, E-S; Emile, J-F (1 June 2009). "Is histological diagnosis of primary liver carcinomas with fibrous stroma reproducible among experts?". Journal of Clinical Pathology. 62 (6): 519–524. doi:10.1136/jcp.2008.062620.
  18. ^ a b Levin, Solomon N.; Tomasini, Michael D.; Knox, James; Shirani, Mahsa; Shebl, Bassem; Requena, David; Clark, Jackson; Heissel, Søren; Alwaseem, Hanan; Surjan, Rodrigo; Lahasky, Ron; Molina, Henrik; Torbenson, Michael S.; Lyons, Barbara; Migler, Rachael D.; Coffino, Philip; Simon, Sanford M. (23 June 2023). "Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma". Science Advances. 9 (25). doi:10.1126/sciadv.adg7038. PMC 10284549.
  19. ^ a b c d e f Berkovitz, Amichai; Migler, Rachael D.; Qureshi, Adam; Rosemore, Carly; Torbenson, Michael S.; Vaughan, Roger; Marcotte, Erin; Simon, Sanford M. (December 2022). "Clinical and demographic predictors of survival for fibrolamellar carcinoma patients—A patient community, registry‐based study". Hepatology Communications. 6 (12): 3539–3549. doi:10.1002/hep4.2105. PMC 9701473.
  20. ^ a b Simon, Sanford M. (May 2023). "Fighting rare cancers: lessons from fibrolamellar hepatocellular carcinoma". Nature Reviews Cancer. 23 (5): 335–346. doi:10.1038/s41568-023-00554-w. PMC 10022574.
  21. ^ "What is Fibrolamellar Carcinoma?". Fibrolamellar Cancer Foundation. Retrieved 2023-01-10.
  22. ^ a b c "Home". The Fibrolamellar Registry.
  23. ^ Chen, Krista Y.; Popovic, Aleksandra; Hsiehchen, David; Baretti, Marina; Griffith, Paige; Bista, Ranjan; Baghdadi, Azarakhsh; Kamel, Ihab R.; Simon, Sanford M.; Migler, Rachael D.; Yarchoan, Mark (30 October 2022). "Clinical Outcomes in Fibrolamellar Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors". Cancers. 14 (21): 5347. doi:10.3390/cancers14215347. PMC 9655068.
  24. ^ Shebl, Bassem; Ng, Denise; Lalazar, Gadi; Rosemore, Carly; Finkelstein, Tova M.; Migler, Rachael D.; Zheng, Guangrong; Zhang, Peiyi; Jiang, Caroline S.; Qureshi, Adam; Vaughan, Roger; Yarchoan, Mark; de Jong, Ype P.; Rice, Charles M.; Coffino, Philip; Ortiz, Michael V.; Zhou, Daohong; Simon, Sanford M. (8 September 2022). "Targeting BCL-XL in fibrolamellar hepatocellular carcinoma". JCI Insight. 7 (17). doi:10.1172/jci.insight.161820. PMC 9536265.
  25. ^ "Fibrolamellar treatment options". Fibrolamellar Cancer Foundation. Retrieved 2023-01-10.
  26. ^ Lafaro KJ, Pawlik TM (2015) Fibrolamellar hepatocellular carcinoma: current clinical perspectives. J Hepatocell Carcinoma 2:151–157 doi: 10.2147/JHC.S75153
  27. ^ Stipa F, Yoon SS, Liau KH, et al. (March 2006). "Outcome of patients with fibrolamellar hepatocellular carcinoma". Cancer. 106 (6): 1331–8. doi:10.1002/cncr.21703. PMID 16475212.
  28. ^ Edmondson HA (1956) Differential diagnosis of tumors and tumor-like lesions of liver in infancy and childhood. AMA J Dis Child 91(2):168–186
  29. ^ Craig JR, Peters RL, Edmondson HA, Omata M. Fibrolamellar carcinoma of the liver: a tumor of adolescents and young adults with distinctive clinico-pathologic features. Cancer 46(2):372–379
  30. ^ Bosman FT (2010) World Health Organization. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon: International Agency for Research on Cancer
  31. ^ "Teen Makes Genetic Discovery of Her Own Rare Cancer". NBC News. 16 April 2014.
  32. ^ "Fibrolamellar Liver Cancer Research".
  33. ^ "Senate Appropriation Hearings on the NIH: Francis Collins".
  34. ^ "Launching of the Precision Medicine Initiative Jan 30, 2015".

External links

August 22, 2023
fibrolamellar, hepatocellular, carcinoma, fibrolamellar, carcinoma, rare, form, carcinoma, that, typically, affects, young, adults, characterized, under, microscope, laminated, fibrous, layers, interspersed, between, tumor, cells, been, estimated, that, cases,. Fibrolamellar carcinoma FLC is a rare form of carcinoma that typically affects young adults and is characterized under the microscope by laminated fibrous layers interspersed between the tumor cells 1 It has been estimated that 200 new cases are diagnosed worldwide each year 2 However in light of recent advances in our molecular understanding this has recently been revised to suggest it may be at least ten times more common 3 FLC also known as fibrolamellar hepatocellular carcinoma is different from the more common hepatocellular carcinoma HCC in that it afflicts young people with normal liver function and no known risk factors 1 2 4 5 Fibrolamellar hepatocellular carcinomaOther namesFHCCMicrograph of fibrolamellar hepatocarcinoma showing the characteristic laminated fibrosis between the tumor cells with a low NC ratio H amp E stain SpecialtyOncology Contents 1 Cause 2 Pathology 3 Diagnosis 4 Treatment 5 Epidemiology 6 History 7 Additional images 8 References 9 External linksCause EditA 2014 study showed the presence of the DNAJB1 PRKACA chimeric transcript resulting from a 400kb somatic deletion on chromosome 19 in 100 of the FLCs examined 15 15 6 7 This gene fusion has been confirmed in many other studies 8 9 10 That this genomic deletion is sufficient to produce FLC was shown by creating this deletion and formation of the DNAJB1 PRKACA chimeric gene using CRISPR Cas9 in the livers of mice 11 12 That the actual formation of the DNAJB1 PRKACA was responsible and not the deletion was shown by expression of the DNAJB1 PRKACA from a transposon 11 To determine if the DNAJB1 PRKACA was only involved in triggering the tumor or if it continued to drive the tumor a small hairpin RNA was used to eliminate the DNAJB1 PRKACA The tumors died which demonstrated not only that DNAJB1 PRKACA is continuing to drive FLC but that the tumor has become oncogenically addicted 13 Pathology EditThe histopathology of FLC is characterized by laminated fibrous layers interspersed between the tumor cells Cytologically the tumor cells have a low nuclear to cytoplasmic ratio with abundant eosinophilic cytoplasm 1 Tumors are non encapsulated but well circumscribed when compared to conventional HCC which typically has an invasive border citation needed Diagnosis EditDue to lack of symptoms until the tumor is sizable this form of cancer is often advanced when diagnosed Symptoms include vague abdominal pain nausea abdominal fullness malaise and weight loss They may also include a palpable liver mass 14 Other presentations include jaundice ascites fulminant liver failure encephalopathy gynecomastia males only thrombophlebitis of the lower limbs recurrent deep vein thrombosis anemia and hypoglycemia citation needed The usual markers for liver disease aspartate aminotransferase alanine aminotransferase and alkaline phosphatase are often normal or only slightly elevated FLC often does not produce alpha fetoprotein AFP a widely used marker for conventional hepatocellular carcinoma In a subset of FLC patients elevated plasma neurotensin levels may be present 15 Likewise in a subset of FLC patients elevated serum vitamin B12 binding globulin levels may be present 16 Diagnosis is normally made by imaging ultrasound CT or MRI and biopsy 17 However even with a biopsy there is often disagreement over the diagnosis 17 Since the characterization of the DNAJB1 PRKACA fusion the most reliable diagnosis is through molecular characterization such as PCR to detect the fusion 7 18 or genomic sequencing or using a fluorescent in situ hybridization 8 Treatment EditFLC can often be surgically removed Liver resection is the optimal treatment and may need to be performed more than once since this disease has a very high recurrence rate 19 Due to such recurrence periodic follow up medical imaging CT or MRI is necessary 19 When the tumor cannot be removed surgically or when there is distant spread many different systemic therapies are currently being used to treat the disease However no standard of care currently exists for FLC Consequently there remains a pressing need to identify proven effective systemic therapies for the cancer 2 20 21 Radiotherapy has been used but data is limited concerning its use The Fibrolamellar Registry http fibroregistry org 22 a patient and family run medical registry has collected data from over 250 patients This work has been used in multiple publications which include extended information on patient outcomes efficacy of immune checkpoint inhibitors efficacy of specific drugs and understanding the basis of high ammonia in FLC 19 23 24 18 The Fibroregistry 22 has answers to frequently asked questions https fibroregistry org faq fibrolamellar as well as plain language summaries of the science literature for understanding the success rate of some treatment approaches https fibroregistry org published papers The FibroFoundation has resources available on different FLC treatment options 25 The survival rate for FLC largely depends on whether and to what degree the cancer has metastasized i e spread to the lymph nodes or other organs Distant spread metastases significantly reduces the median survival rate 19 Five year survival rates vary between 40 90 19 Epidemiology EditFLC accounts for 1 10 of primary liver cancers 26 It typically has a young age at presentation when compared to conventional HCC Previously it was estimated to be 20 40 years mean ages 27 years 27 but when analysis is restricted to those patients who are confirmed with a molecular test to have FLC the age range is 10 40 and mean age of 21 years 19 Unlike the more common HCC patients most often do not have coexistent liver disease such as cirrhosis History EditThis disease was first described by Hugh Edmondson in a 14 year old female with no underlying liver disease 28 The name fibrolamellar hepatocellular carcinoma was coined by Craig et al in 1980 29 It was not recognized as a distinct form of cancer by the WHO until 2010 30 Starting in 2010 some patients and their family members started to examine the molecular basis of FLC 20 They gathered samples through social media 31 32 sequenced the genome and analyzed the immunological response Since there are few patients at any one institution they formed their own medical registry which allowed them to follow patients as they changed institutions http fibroregistry org 22 This work led to the identification of the chimeric fusion driver and the first characterization of the transcriptome and proteome The work was heralded by Francis Collins when he presented to the Senate Appropriations committee 33 and was used by President Obama at the launch of The Precision Medicine Initiative at the White House 34 Additional images Edit Intermed mag High mag References Edit a b c Torbenson Michael 2012 Fibrolamellar Carcinoma 2012 Update Scientifica 2012 1 15 doi 10 6064 2012 743790 PMC 3820672 a b c O Neill Allison F Church Alanna J Perez Atayde Antonio R Shaikh Raja Marcus Karen J Vakili Khashayar August 2021 Fibrolamellar carcinoma An entity all its own Current Problems in Cancer 45 4 100770 doi 10 1016 j currproblcancer 2021 100770 Zack Travis Losert Kurt P Maisel Samantha M Wild Jennifer Yaqubie Amin Herman Michael Knox Jennifer J Mayer Robert J Venook Alan P Butte Atul O Neill Allison F Abou Alfa Ghassan K Gordan John D 23 March 2023 Defining incidence and complications of fibrolamellar liver cancer through tiered computational analysis of clinical data npj Precision Oncology 7 1 doi 10 1038 s41698 023 00371 2 Lalazar Gadi Simon Sanford February 2018 Fibrolamellar Carcinoma Recent Advances and Unresolved Questions on the Molecular Mechanisms Seminars in Liver Disease 38 01 051 059 doi 10 1055 s 0037 1621710 PMC 6020845 What is Fibrolamellar Carcinoma Fibrolamellar Cancer Foundation Retrieved 2023 01 10 Teen Makes Genetic Discovery of Her Own Rare Cancer a b Honeyman JN Simon EP Robine N Chiaroni Clarke R Darcy DG Lim II Gleason CE Murphy JM Rosenberg BR Teegan L Takacs CN Botero S Belote R Germer S Emde AK Vacic V Bhanot U LaQuaglia MP Simon SM 28 February 2014 Detection of a Recurrent DNAJB1 PRKACA Chimeric Transcript in Fibrolamellar Hepatocellular Carcinoma Science 343 6174 1010 4 Bibcode 2014Sci 343 1010H doi 10 1126 science 1249484 PMC 4286414 PMID 24578576 a b Graham Rondell P Jin Long Knutson Darlene L Kloft Nelson Sara M Greipp Patricia T Waldburger Nina Roessler Stephanie Longerich Thomas Roberts Lewis R Oliveira Andre M Halling Kevin C Schirmacher Peter Torbenson Michael S June 2015 DNAJB1 PRKACA is specific for fibrolamellar carcinoma Modern Pathology 28 6 822 829 doi 10 1038 modpathol 2015 4 Xu Lei Hazard Florette K Zmoos Anne Flore Jahchan Nadine Chaib Hassan Garfin Phillip M Rangaswami Arun Snyder Michael P Sage Julien 1 January 2015 Genomic analysis of fibrolamellar hepatocellular carcinoma Human Molecular Genetics 24 1 50 63 doi 10 1093 hmg ddu418 PMC 4262492 Dinh TA Vitucci EC Wauthier E Graham RP Pitman WA Oikawa T Chen M Silva G Greene KG Torbenson MS Reid LM Sethupathy P 2017 Comprehensive analysis of The Cancer Genome Atlas reveals a unique gene and non coding RNA signature of fibrolamellar carcinoma Sci Rep 7 44653 doi 10 1038 srep44653 a b Kastenhuber Edward R Lalazar Gadi Houlihan Shauna L Tschaharganeh Darjus F Baslan Timour Chen Chi Chao Requena David Tian Sha Bosbach Benedikt Wilkinson John E Simon Sanford M Lowe Scott W 12 December 2017 DNAJB1 PRKACA fusion kinase interacts with b catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma Proceedings of the National Academy of Sciences 114 50 13076 13084 doi 10 1073 pnas 1716483114 PMC 5740683 Engelholm Lars H Riaz Anjum Serra Denise Dagnaes Hansen Frederik Johansen Jens V Santoni Rugiu Eric Hansen Steen H Niola Francesco Frodin Morten December 2017 CRISPR Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1 Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma Gastroenterology 153 6 1662 1673 e10 doi 10 1053 j gastro 2017 09 008 Neumayer Christoph Ng Denise Jiang Caroline S Qureshi Adam Lalazar Gadi Vaughan Roger Simon Sanford M 4 January 2023 Oncogenic Addiction of Fibrolamellar Hepatocellular Carcinoma to the Fusion Kinase DNAJB1 PRKACA Clinical Cancer Research 29 1 271 278 doi 10 1158 1078 0432 CCR 22 1851 PMC 9811160 Yen JB Chang KW 2009 Fibrolamellar hepatocellular carcinoma report of a case Chang Gung Med J 32 3 336 9 PMID 19527614 Collier N A Bloom S R Hodgson H J F Weinbren K Lee Y C Blumgart L H March 1984 NEUROTENSIN SECRETION BY FIBROLAMELLAR CARCINOMA OF THE LIVER The Lancet 323 8376 538 540 doi 10 1016 s0140 6736 84 90934 6 Paradinas F J Melia W M Wilkinson M L Portmann B Johnson P J Murray Lyon I M Williams R 25 September 1982 High serum vitamin B12 binding capacity as a marker of the fibrolamellar variant of hepatocellular carcinoma BMJ 285 6345 840 842 doi 10 1136 bmj 285 6345 840 PMC 1499744 a b Malouf G Falissard B Azoulay D Callea F Ferrell L D Goodman Z D Hayashi Y Hsu H C Hubscher S G Kojiro M Ng I O Paterson A C Reynes M Zafrani E S Emile J F 1 June 2009 Is histological diagnosis of primary liver carcinomas with fibrous stroma reproducible among experts Journal of Clinical Pathology 62 6 519 524 doi 10 1136 jcp 2008 062620 a b Levin Solomon N Tomasini Michael D Knox James Shirani Mahsa Shebl Bassem Requena David Clark Jackson Heissel Soren Alwaseem Hanan Surjan Rodrigo Lahasky Ron Molina Henrik Torbenson Michael S Lyons Barbara Migler Rachael D Coffino Philip Simon Sanford M 23 June 2023 Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma Science Advances 9 25 doi 10 1126 sciadv adg7038 PMC 10284549 a b c d e f Berkovitz Amichai Migler Rachael D Qureshi Adam Rosemore Carly Torbenson Michael S Vaughan Roger Marcotte Erin Simon Sanford M December 2022 Clinical and demographic predictors of survival for fibrolamellar carcinoma patients A patient community registry based study Hepatology Communications 6 12 3539 3549 doi 10 1002 hep4 2105 PMC 9701473 a b Simon Sanford M May 2023 Fighting rare cancers lessons from fibrolamellar hepatocellular carcinoma Nature Reviews Cancer 23 5 335 346 doi 10 1038 s41568 023 00554 w PMC 10022574 What is Fibrolamellar Carcinoma Fibrolamellar Cancer Foundation Retrieved 2023 01 10 a b c Home The Fibrolamellar Registry Chen Krista Y Popovic Aleksandra Hsiehchen David Baretti Marina Griffith Paige Bista Ranjan Baghdadi Azarakhsh Kamel Ihab R Simon Sanford M Migler Rachael D Yarchoan Mark 30 October 2022 Clinical Outcomes in Fibrolamellar Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors Cancers 14 21 5347 doi 10 3390 cancers14215347 PMC 9655068 Shebl Bassem Ng Denise Lalazar Gadi Rosemore Carly Finkelstein Tova M Migler Rachael D Zheng Guangrong Zhang Peiyi Jiang Caroline S Qureshi Adam Vaughan Roger Yarchoan Mark de Jong Ype P Rice Charles M Coffino Philip Ortiz Michael V Zhou Daohong Simon Sanford M 8 September 2022 Targeting BCL XL in fibrolamellar hepatocellular carcinoma JCI Insight 7 17 doi 10 1172 jci insight 161820 PMC 9536265 Fibrolamellar treatment options Fibrolamellar Cancer Foundation Retrieved 2023 01 10 Lafaro KJ Pawlik TM 2015 Fibrolamellar hepatocellular carcinoma current clinical perspectives J Hepatocell Carcinoma 2 151 157 doi 10 2147 JHC S75153 Stipa F Yoon SS Liau KH et al March 2006 Outcome of patients with fibrolamellar hepatocellular carcinoma Cancer 106 6 1331 8 doi 10 1002 cncr 21703 PMID 16475212 Edmondson HA 1956 Differential diagnosis of tumors and tumor like lesions of liver in infancy and childhood AMA J Dis Child 91 2 168 186 Craig JR Peters RL Edmondson HA Omata M Fibrolamellar carcinoma of the liver a tumor of adolescents and young adults with distinctive clinico pathologic features Cancer 46 2 372 379 Bosman FT 2010 World Health Organization WHO Classification of Tumours of the Digestive System 4th ed Lyon International Agency for Research on Cancer Teen Makes Genetic Discovery of Her Own Rare Cancer NBC News 16 April 2014 Fibrolamellar Liver Cancer Research Senate Appropriation Hearings on the NIH Francis Collins Launching of the Precision Medicine Initiative Jan 30 2015 External links Edit Retrieved from https en wikipedia org w index php title Fibrolamellar hepatocellular carcinoma amp oldid 1169947932, wikipedia, wiki, book, books, library,

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