Molecular detection and clinicopathological characteristics of advanced/recurrent biliary tract carcinomas harboring the FGFR2 rearrangements: a prospective observational study (PRELUDE Study).
Advanced/recurrent biliary tract cancer
FGFR2 rearrangement
Fluorescent in situ hybridization
RNA sequencing
Journal
Journal of gastroenterology
ISSN: 1435-5922
Titre abrégé: J Gastroenterol
Pays: Japan
ID NLM: 9430794
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
11
05
2020
accepted:
26
09
2020
pubmed:
28
10
2020
medline:
15
12
2021
entrez:
27
10
2020
Statut:
ppublish
Résumé
Fibroblast growth factor receptor 2 (FGFR2) rearrangement is expected to be a novel therapeutic target in advanced/recurrent biliary tract cancer (BTC). However, efficient detection and the exact frequency of FGFR2 rearrangements among patients with advanced/recurrent BTC have not been determined, and the clinical characteristics of FGFR2 rearrangement-positive patients have not been fully elucidated. We aimed to determine the frequency of FGFR2 rearrangement-positive patients among those with advanced/recurrent BTC and elucidate their clinicopathological characteristics. Paraffin-embedded tumor samples from formalin-fixed surgical or biopsy specimens of patients with advanced/recurrent BTC were analyzed for positivity of FGFR2 rearrangement by fluorescent in situ hybridization (FISH). RNA sequencing was performed on samples from all FISH-positive and part of FISH-negative patients. A total of 445 patients were enrolled. FISH was performed on 423 patients (272 patients with intrahepatic cholangiocarcinoma (ICC), 83 patients with perihilar cholangiocarcinoma (PCC), and 68 patients with other BTC). Twenty-one patients with ICC and four patients with PCC were diagnosed as FGFR2-FISH positive. Twenty-three of the 25 FISH-positive patients (20 ICC and 3 PCC) were recognized as FGFR2 rearrangement positive by targeted RNA sequencing. Younger age (≤ 65 years; p = 0.018) and HCV Ab- and/or HBs Ag-positivity (p = 0.037) were significantly associated with the presence of FGFR2 rearrangement (logistic regression). FGFR2 rearrangement was identified in ICC and PCC patients, and was associated with younger age and history of hepatitis viral infection.
Sections du résumé
BACKGROUND
Fibroblast growth factor receptor 2 (FGFR2) rearrangement is expected to be a novel therapeutic target in advanced/recurrent biliary tract cancer (BTC). However, efficient detection and the exact frequency of FGFR2 rearrangements among patients with advanced/recurrent BTC have not been determined, and the clinical characteristics of FGFR2 rearrangement-positive patients have not been fully elucidated. We aimed to determine the frequency of FGFR2 rearrangement-positive patients among those with advanced/recurrent BTC and elucidate their clinicopathological characteristics.
METHODS
Paraffin-embedded tumor samples from formalin-fixed surgical or biopsy specimens of patients with advanced/recurrent BTC were analyzed for positivity of FGFR2 rearrangement by fluorescent in situ hybridization (FISH). RNA sequencing was performed on samples from all FISH-positive and part of FISH-negative patients.
RESULTS
A total of 445 patients were enrolled. FISH was performed on 423 patients (272 patients with intrahepatic cholangiocarcinoma (ICC), 83 patients with perihilar cholangiocarcinoma (PCC), and 68 patients with other BTC). Twenty-one patients with ICC and four patients with PCC were diagnosed as FGFR2-FISH positive. Twenty-three of the 25 FISH-positive patients (20 ICC and 3 PCC) were recognized as FGFR2 rearrangement positive by targeted RNA sequencing. Younger age (≤ 65 years; p = 0.018) and HCV Ab- and/or HBs Ag-positivity (p = 0.037) were significantly associated with the presence of FGFR2 rearrangement (logistic regression).
CONCLUSIONS
FGFR2 rearrangement was identified in ICC and PCC patients, and was associated with younger age and history of hepatitis viral infection.
Identifiants
pubmed: 33106918
doi: 10.1007/s00535-020-01735-2
pii: 10.1007/s00535-020-01735-2
pmc: PMC7932978
doi:
Substances chimiques
FGFR2 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 2
EC 2.7.10.1
Types de publication
Journal Article
Multicenter Study
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
250-260Commentaires et corrections
Type : ErratumIn
Références
Cancer Statistics in Japan 2018, The Editorial Board of the Cancer Statistics in Japan
Rizvi S, Khan SA, Hallemeier CL, et al. Cholangiocarcinoma—evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15:95–111.
doi: 10.1038/nrclinonc.2017.157
Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.
doi: 10.1056/NEJMoa0908721
Valle JW, Lamarca A, Goyal L, et al. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017;7:943–62.
doi: 10.1158/2159-8290.CD-17-0245
Kipp BR, Voss JS, Kerr SE, et al. Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Hum Pathol. 2012;43:1552–8.
doi: 10.1016/j.humpath.2011.12.007
Abou-Alfa GK, Macarulla Mercade T, Javle M, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:796–807.
doi: 10.1016/S1470-2045(20)30157-1
Borad MJ, Gores GJ, Roberts LR. Fibroblast growth factor receptor 2 fusions as a target for treating cholangiocarcinoma. Curr Opin Gastroenterol. 2015;31:264–8.
doi: 10.1097/MOG.0000000000000171
Javle M, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced Cholangiocarcinoma. J Clin Oncol. 2018;36:276–82.
doi: 10.1200/JCO.2017.75.5009
Hollebecque A, Borad M, Sahai V, et al. Interim results of fight-202, a phase II open-label multicenter study of INCB054828 in patients (pts) with previously treated advanced/metastatic or surgically unresectable cholangiocarcinoma (CCA) with/without fibroblast growth factor (FGF)/FGF receptor (FGFR) genetic alterations. Ann Oncol. 2018;29(8):258. https://doi.org/10.1093/annonc/mdy282.139 .
doi: 10.1093/annonc/mdy282.139
Brooks AN, Kilgour E, Smith PD. Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer. Clin Cancer Res. 2012;18:1855–62.
doi: 10.1158/1078-0432.CCR-11-0699
Mahipal A, Tella SH, Kommalapati A, et al. FGFR2 genomic aberrations: Achilles heel in the management of advanced cholangiocarcinoma. Cancer Treat Rev. 2019;78:1–7.
doi: 10.1016/j.ctrv.2019.06.003
Arai Y, Totoki Y, Hosoda F, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59:1427–34.
doi: 10.1002/hep.26890
Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671–84.
doi: 10.1016/S1470-2045(20)30109-1
Graham RP, Barr Fritcher EG, Pestova E, et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol. 2014;45:1630–8.
doi: 10.1016/j.humpath.2014.03.014
Weiss GJ, Hoff BR, Whitehead RP, et al. Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision making. Onco Targets Ther. 2015;8:959–67.
doi: 10.2147/OTT.S81995
Nakamura H, Arai Y, Totoki Y, et al. Genomic spectra of biliary tract cancer. Nat Genet. 2015;47:1003–100.
doi: 10.1038/ng.3375
Jain A, Borad MJ, Kelley RK, et al. Cholangiocarcinoma with FGFR genetic aberrations: a unique clinical phenotype. JCO Precis Oncol. 2018;2:1–12.
Churi CR, Shroff R, Wang Y, et al. Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PLoS ONE. 2014;9:e115383.
doi: 10.1371/journal.pone.0115383
Hayashi A, Misumi K, Shibahara J, et al. Distinct clinicopathologic and genetic features of 2 histologic subtypes of intrahepatic cholangiocarcinoma. Am J Surg Pathol. 2016;40:1021–30.
doi: 10.1097/PAS.0000000000000670
Hirata K, Kuwatani M, Suda G, et al. A novel approach for the genetic analysis of biliary tract cancer specimens obtained through endoscopic ultrasound-guided fine needle aspiration using targeted amplicon sequencing. Clin Transl Gastroenterol. 2019;10:e00022.
doi: 10.14309/ctg.0000000000000022
Jusakul A, Cutcutache I, Yong CH, et al. Whole-Genome and epigenomic landscapes of etiologically distinct subtypes of Cholangiocarcinoma. Cancer Discov. 2017;7:1116–35.
doi: 10.1158/2159-8290.CD-17-0368
Cha JY, Maddileti S, Mitin N, et al. Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform. J Biol Chem. 2009;284:6227–400.
doi: 10.1074/jbc.M803998200
Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res. 2018;24:4154–61.
doi: 10.1158/1078-0432.CCR-18-0078
Tang Z, Wang L, Tang G, et al. Fluorescence in situ hybridization (FISH) for detecting anaplastic lymphoma kinase (ALK) rearrangement in lung cancer: clinically relevant technical aspects. Int J Mol Sci. 2019;20:3939.
doi: 10.3390/ijms20163939
Soria JC, Ho SN, Varella-Garcia M, et al. Correlation of extent of ALK FISH positivity and crizotinib efficacy in three prospective studies of ALK-positive patients with non-small-cell lung cancer. Ann Oncol. 2018;29:1964–71.
doi: 10.1093/annonc/mdy242
Joseph NM, Tsokos CG, Umetsu SE, et al. Genomic profiling of combined hepatocellular-cholangiocarcinoma reveals similar genetics to hepatocellular carcinoma. J Pathol. 2019;248:164–78.
doi: 10.1002/path.5243
Palmer WC, Patel T. Are common factors involved in the pathogenesis of primary liver cancers? a meta-analysis of risk factors for intrahepatic cholangiocarcinoma. J Hepatol. 2012;57:69–766.
doi: 10.1016/j.jhep.2012.02.022
Li M, Li J, Li P, et al. Hepatitis B virus infection increases the risk of cholangiocarcinoma: a meta-analysis and systematic review. J Gastroenterol Hepatol. 2012;27:1561–8.
doi: 10.1111/j.1440-1746.2012.07207.x