<em>ROS1</em> rearrangements are uncommon in biliary tract cancers

Mazzoni,Francesca; Petreni,Paolo; Vasile,Enrico; Panebianco,Michele; Casadei‑Gardini,Andrea; Negri,Francesca; Lunghi,Alice; Pillozzi,Serena; Vivaldi,Caterina; Gervasi,Erika; Frassineti,Giovanni Luca; Messerini,Luca; Jocollé,Genny; Bisagni,Alessandra; Antonuzzo,Lorenzo; Rossi,Giulio

doi:10.3892/ol.2020.12179

ROS1 rearrangements are uncommon in biliary tract cancers

Authors:
- Francesca Mazzoni
- Paolo Petreni
- Enrico Vasile
- Michele Panebianco
- Andrea Casadei‑Gardini
- Francesca Negri
- Alice Lunghi
- Serena Pillozzi
- Caterina Vivaldi
- Erika Gervasi
- Giovanni Luca Frassineti
- Luca Messerini
- Genny Jocollé
- Alessandra Bisagni
- Lorenzo Antonuzzo
- Giulio Rossi
View Affiliations

Affiliations: Medical Oncology Unit, AOU Careggi Hospital, I‑50134 Florence, Italy, Medical Oncology Unit, Alta Val d'Elsa Hospital, I‑53036 Poggibonsi, Italy, Medical Oncology Unit, AOU Pisana Hospital, I‑56126 Pisa, Italy, AUSL‑IRCSS, I‑42122 Reggio Emilia, Italy, Department of Medical Oncology, IRST IRCCS, I‑47014 Meldola, Italy, Medical Oncology Unit, AOU Parma Hospital, I‑43126 Parma, Italy, Medical Oncology Unit, San Luca Hospital, I‑55100 Lucca, Italy, Anatomical Pathology Unit, AOU Careggi Hospital, I‑50134 Florence, Italy, Regional Parini Hospital, I‑11100 Aosta, Italy, Pathology Unit, ASL‑IRCCS, I‑42122 Reggio Emilia, Italy, Operative Unit of Pathologic Anatomy, Santa Maria delle Croci Hospital, I‑48121 Ravenna, Italy
Published online on: October 1, 2020 https://doi.org/10.3892/ol.2020.12179
Article Number: 316

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Biliary tract cancers (BTCs) are a pool of diseases with poor prognosis and there is no orphan drug available. Currently, no molecular targets have been tested as druggable oncogenic drivers. C‑ros oncogene 1 (ROS1) rearrangements have been previously described in various tumors, including BTCs; however, data regarding their incidence and biological significance are controversial. Therefore, a retrospective multicenter study was performed to assess the incidence of ROS1 rearrangements in BTCs by means of immunohistochemistry and fluorescence in situ hybridization (FISH). The present study failed to demonstrate ROS1 expression in a multicenter series of 150 cases with BTCs and revealed that D4D6 was the most specific clone compared with other ROS1 primary antibodies, namely PA1‑30318 and EPMGHR2. Notably, negative results obtained with D4D6 completely matched to data sorted out by FISH analysis, thus confirming a lack of ROS1 gene rearrangements in BTCs and false positive results when PA1‑30318 and EPMGHR2 clones were used. These results suggest that ROS1 rearrangements may not be targets for molecular therapy of BTCs with specific inhibitors.

View Figures

View References

1	Italian Association Medical Oncology association tumor register. The numbers of cancer in Italy. 2017, simplehttp://www.registri-tumori.it/cms/pubblicazioni/i-numeri-del-cancro-italia-2017Published September, 2017. July 6–2018
2	Huguet JM, Lobo M, Labrador JM, Boix C, Albert C, Ferrer-Barceló L, Durá AB, Suárez P, Iranzo I, Gil-Raga M, et al: Diagnostic-therapeutic management of bile duct cancer. World J Clin Cases. 7:1732–1752. 2019. View Article : Google Scholar : PubMed/NCBI
3	Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T and Svensson C: Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 7:593–600. 1996. View Article : Google Scholar : PubMed/NCBI
4	Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, et al ABC-02 Trial Investigators, : Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 362:1273–1281. 2010. View Article : Google Scholar : PubMed/NCBI
5	Jain A and Javle M: Molecular profiling of biliary tract cancer: A target rich disease. J Gastrointest Oncol. 7:797–803. 2016. View Article : Google Scholar : PubMed/NCBI
6	Jusakul A, Cutcutache I, Yong CH, Lim JQ, Huang MN, Padmanabhan N, Nellore V, Kongpetch S, Ng AWT, Ng LM, et al: Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma. Cancer Discov. 7:1116–1135. 2017. View Article : Google Scholar : PubMed/NCBI
7	Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, Ramanathan RK, Goyal L, Sadeghi S, Macarulla T, et al: Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma. J Clin Oncol. 36:276–282. 2018. View Article : Google Scholar : PubMed/NCBI
8	Goyal L, Arkenau HT, Tran B, Soria J-C, Bahleda R, Mak G, Zhu A, Javle M, Hiroshi H, Benedetti F, et al: Early clinical efficacy of TAS-120, a covalently bound FGFR inhibitor, in patients with cholangiocarcinoma. Ann Oncol. 28 (Suppl 3):202017. View Article : Google Scholar
9	Blair AB and Murphy A: Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future. Curr Probl Cancer. 42:49–58. 2018. View Article : Google Scholar : PubMed/NCBI
10	Davies KD and Doebele RC: Molecular pathways: ROS1 fusion proteins in cancer. Clin Cancer Res. 19:4040–4045. 2013. View Article : Google Scholar : PubMed/NCBI
11	Uguen A and De Braekeleer M: ROS1 fusions in cancer: A review. Future Oncol. 12:1911–1928. 2016. View Article : Google Scholar : PubMed/NCBI
12	Bansal M, He J, Peyton M, Kustagi M, Iyer A, Comb M, White M, Minna JD and Califano A: Elucidating synergistic dependencies in lung adenocarcinoma by proteome-wide signaling-network analysis. PLoS One. 14:e02086462019. View Article : Google Scholar : PubMed/NCBI
13	Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, McDonald NT, Massion PP, Siwak-Tapp C, Gonzalez A, Fang R, et al: ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 30:863–870. 2012. View Article : Google Scholar : PubMed/NCBI
14	Jänne PA and Meyerson M; J2012 PA, : ROS1 rearrangements in lung cancer: A new genomic subset of lung adenocarcinoma. J Clin Oncol. 30:878–879. 2012. View Article : Google Scholar : PubMed/NCBI
15	Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, et al: Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 371:1963–1971. 2014. View Article : Google Scholar : PubMed/NCBI
16	Mazières J, Zalcman G, Crinò L, Biondani P, Barlesi F, Filleron T, Dingemans AM, Léna H, Monnet I, Rothschild SI, et al: Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort. J Clin Oncol. 33:992–999. 2015. View Article : Google Scholar : PubMed/NCBI
17	Chiari R, Buttitta F, Iacono D, Bennati C, Metro G, Di Lorito A, Iezzi M, Tiseo M, Mazzoni F, Cappuzzo F, et al: Dramatic response to crizotinib in ROS1 fluorescent in situ hybridization- and immunohistochemistry-positive lung adenocarcinoma: a case series. Clin Lung Cancer. 15:470–474. 2014. View Article : Google Scholar : PubMed/NCBI
18	Landi L, Chiari R, Tiseo M, D'Incà F, Dazzi C, Chella A, Delmonte A, Bonanno L, Giannarelli D, Cortinovis DL, et al: Crizotinib in MET-Deregulated or ROS1-Rearranged Pretreated Non-Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial. Clin Cancer Res. 25:7312–7319. 2019. View Article : Google Scholar : PubMed/NCBI
19	Petreni P, Mazzoni F, Meoni G, Lunghi A, Cecere FL, Muto A and Di Costanzo F: Outcome of crizotinib treatment in a young woman with heavily pretreated ROS1-positive lung cancer. Tumori. 101:e103–e106. 2015. View Article : Google Scholar : PubMed/NCBI
20	Gu TL, Deng X, Huang F, Tucker M, Crosby K, Rimkunas V, Wang Y, Deng G, Zhu L, Tan Z, et al: Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma. PLoS One. 6:e156402011. View Article : Google Scholar : PubMed/NCBI
21	Liu P, Wu Y, Sun L, Zuo Q and Shi M: ROS kinase fusions are not common in Chinese patients with cholangiocarcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 33:474–478. 2013.PubMed/NCBI
22	Graham RP, Barr Fritcher EG, Pestova E, Schulz J, Sitailo LA, Vasmatzis G, Murphy SJ, McWilliams RR, Hart SN, Halling KC, et al: Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol. 45:1630–1638. 2014. View Article : Google Scholar : PubMed/NCBI
23	Kipp BR, Voss JS, Kerr SE, Barr Fritcher EG, Graham RP, Zhang L, Highsmith WE, Zhang J, Roberts LR, Gores GJ, et al: Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Hum Pathol. 43:1552–1558. 2012. View Article : Google Scholar : PubMed/NCBI
24	Lee KH, Lee KB, Kim TY, Han SW, Oh DY, Im SA, Kim TY, Yi NJ, Lee KW, Suh KS, et al: Clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. BMC Cancer. 15:7212015. View Article : Google Scholar : PubMed/NCBI
25	Lim SM, Yoo JE, Lim KH, Meng Tai DW, Cho BC and Park YN: Rare Incidence of ROS1 Rearrangement in Cholangiocarcinoma. Cancer Res Treat. 49:185–192. 2017. View Article : Google Scholar : PubMed/NCBI
26	Rossi G, Jocollé G, Conti A, Tiseo M, Zito Marino F, Donati G, Franco R, Bono F, Barbisan F and Facchinetti F: Detection of ROS1 rearrangement in non-small cell lung cancer: Current and future perspectives. Lung Cancer (Auckl). 8:45–55. 2017.PubMed/NCBI
27	Conde E, Hernandez S, Martinez R, De Castro J, Collazo-Lorduy A, Jimenez B, Muriel A, Mate JL, Morán T, Aranda I, et al: Evaluation of a Novel ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in NSCLC Patients. J Thorac Oncol. 13 (Suppl 10):S553–S554. 2018. View Article : Google Scholar
28	Arai Y, Totoki Y, Hosoda F, Shirota T, Hama N, Nakamura H, Ojima H, Furuta K, Shimada K, Okusaka T, et al: Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 59:1427–1434. 2014. View Article : Google Scholar : PubMed/NCBI
29	Bubendorf L, Büttner R, Al-Dayel F, Dietel M, Elmberger G, Kerr K, López-Ríos F, Marchetti A, Öz B, Pauwels P, et al: Testing for ROS1 in non-small cell lung cancer: A review with recommendations. Virchows Arch. 469:489–503. 2016. View Article : Google Scholar : PubMed/NCBI
30	Abou-Alfa GK, Andersen JB, Chapman W, Choti M, Forbes SJ, Gores GJ, Hong TS, Harding JJ, Vander Heiden MG, Javle M, et al: Advances in cholangiocarcinoma research: Report from the third Cholangiocarcinoma Foundation Annual Conference. J Gastrointest Oncol. 7:819–827. 2016. View Article : Google Scholar : PubMed/NCBI
31	Lowery MA, Ptashkin R, Jordan E, Berger MF, Zehir A, Capanu M, Kemeny NE, O'Reilly EM, El-Dika I, Jarnagin WR, et al: Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: Potential Targets for Intervention. Clin Cancer Res. 24:4154–4161. 2018. View Article : Google Scholar : PubMed/NCBI