Literature DB >> 33658299

Comprehensive Molecular Characterization and Response to Therapy in Fumarate Hydratase-Deficient Renal Cell Carcinoma.

Jack P Gleeson1, Ines Nikolovski2, Renzo Dinatale3, Mark Zucker3, Andrea Knezevic3, Sujata Patil3, Yasser Ged4, Ritesh R Kotecha1, Natalie Shapnik1, Samuel Murray1, Paul Russo5, Jonathan Coleman5, Chung Han Lee1, Zsofia K Stadler6, A Ari Hakimi5, Darren R Feldman1, Robert J Motzer1, Ed Reznik3, Martin H Voss1, Ying-Bei Chen7, Maria I Carlo8,6.   

Abstract

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare, aggressive form of RCC associated with hereditary leiomyomatosis and RCC syndrome. Evidence for systemic therapy efficacy is lacking. EXPERIMENTAL
DESIGN: We studied clinical and genomic characteristics of FH-RCC, including response [objective response rate (ORR)] to systemic therapies and next-generation sequencing (NGS). Patients with metastatic FH-RCC, defined by presence of pathogenic germline or somatic FH mutation plus IHC evidence of FH loss, were included.
RESULTS: A total of 28 of 32 included patients (median age 46; range, 20-74; M:F, 20:12) underwent germline testing; 23 (82%) harbored a pathogenic FH germline variant. Five (16%) were negative for germline FH mutations; all had biallelic somatic FH loss. Somatic NGS (31/32 patients) revealed co-occurring NF2 mutation most frequently (n = 5). Compared with clear-cell RCC, FH-RCC had a lower mutation count (median 2 vs. 4; P < 0.001) but higher fraction of genome altered (18.7% vs. 10.3%; P = 0.001). A total of 26 patients were evaluable for response to systemic therapy: mTOR/VEGF combination (n = 18, ORR 44%), VEGF monotherapy (n = 15, ORR 20%), checkpoint inhibitor therapy (n = 8, ORR 0%), and mTOR monotherapy (n = 4, ORR 0%). No complete responses were seen. Median overall and progression-free survival were 21.9 months [95% confidence interval (CI): 14.3-33.8] and 8.7 months (95% CI: 4.8-12.3), respectively.
CONCLUSIONS: Although most FH-RCC tumors are due to germline FH alterations, a significant portion result from biallelic somatic FH loss. Both somatic and germline FH-RCC have similar molecular characteristics, with NF2 mutations, low tumor mutational burden, and high fraction of genome altered. Although immunotherapy alone produced no objective responses, combination mTOR/VEGF therapy showed encouraging results. ©2021 American Association for Cancer Research.

Entities:  

Mesh：

Substances：

Year:  2021        PMID： 33658299      PMCID： PMC8127353          DOI： 10.1158/1078-0432.CCR-20-4367

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  40 in total

1.  Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma.

Authors:  Chisato Ohe; Steven C Smith; Deepika Sirohi; Mukul Divatia; Mariza de Peralta-Venturina; Gladell P Paner; Abbas Agaimy; Mitual B Amin; Pedram Argani; Ying-Bei Chen; Liang Cheng; Maurizio Colecchia; Eva Compérat; Isabela Werneck da Cunha; Jonathan I Epstein; Anthony J Gill; Ondřej Hes; Michelle S Hirsch; Wolfram Jochum; Lakshmi P Kunju; Fiona Maclean; Cristina Magi-Galluzzi; Jesse K McKenney; Rohit Mehra; Gabriella Nesi; Adeboye O Osunkoya; Maria M Picken; Priya Rao; Victor E Reuter; Paulo Guilherme de Oliveira Salles; Luciana Schultz; Satish K Tickoo; Scott A Tomlins; Kiril Trpkov; Mahul B Amin
Journal:  Am J Surg Pathol       Date:  2018-03       Impact factor: 6.394

2.  Inherited susceptibility to uterine leiomyomas and renal cell cancer.

Authors:  V Launonen; O Vierimaa; M Kiuru; J Isola; S Roth; E Pukkala; P Sistonen; R Herva; L A Aaltonen
Journal:  Proc Natl Acad Sci U S A       Date:  2001-02-27       Impact factor: 11.205

3.  Tubulocystic Carcinoma of the Kidney With Poorly Differentiated Foci: A Frequent Morphologic Pattern of Fumarate Hydratase-deficient Renal Cell Carcinoma.

Authors:  Steven C Smith; Kiril Trpkov; Ying-Bei Chen; Rohit Mehra; Deepika Sirohi; Chisato Ohe; Andi K Cani; Daniel H Hovelson; Kei Omata; Jonathan B McHugh; Wolfram Jochum; Maurizio Colecchia; Mitual Amin; Mukul K Divatia; Ondřej Hes; Santosh Menon; Isabela Werneck da Cunha; Sergio Tripodi; Fadi Brimo; Anthony J Gill; Adeboye O Osunkoya; Cristina Magi-Galluzzi; Mathilde Sibony; Sean R Williamson; Gabriella Nesi; Maria M Picken; Fiona Maclean; Abbas Agaimy; Liang Cheng; Jonathan I Epstein; Victor E Reuter; Satish K Tickoo; Scott A Tomlins; Mahul B Amin
Journal:  Am J Surg Pathol       Date:  2016-11       Impact factor: 6.394

4.  Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma.

Authors:  Martin H Voss; Ana M Molina; Ying-Bei Chen; Kaitlin M Woo; Joshua L Chaim; Devyn T Coskey; Almedina Redzematovic; Patricia Wang; William Lee; S Duygu Selcuklu; Chung-Han Lee; Michael F Berger; Satish K Tickoo; Victor E Reuter; Sujata Patil; James J Hsieh; Robert J Motzer; Darren R Feldman
Journal:  J Clin Oncol       Date:  2016-11-10       Impact factor: 44.544

5.  Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

Authors:  Diana Mandelker; Liying Zhang; Yelena Kemel; Zsofia K Stadler; Vijai Joseph; Ahmet Zehir; Nisha Pradhan; Angela Arnold; Michael F Walsh; Yirong Li; Anoop R Balakrishnan; Aijazuddin Syed; Meera Prasad; Khedoudja Nafa; Maria I Carlo; Karen A Cadoo; Meg Sheehan; Megan H Fleischut; Erin Salo-Mullen; Magan Trottier; Steven M Lipkin; Anne Lincoln; Semanti Mukherjee; Vignesh Ravichandran; Roy Cambria; Jesse Galle; Wassim Abida; Marcia E Arcila; Ryma Benayed; Ronak Shah; Kenneth Yu; Dean F Bajorin; Jonathan A Coleman; Steven D Leach; Maeve A Lowery; Julio Garcia-Aguilar; Philip W Kantoff; Charles L Sawyers; Maura N Dickler; Leonard Saltz; Robert J Motzer; Eileen M O'Reilly; Howard I Scher; Jose Baselga; David S Klimstra; David B Solit; David M Hyman; Michael F Berger; Marc Ladanyi; Mark E Robson; Kenneth Offit
Journal:  JAMA       Date:  2017-09-05       Impact factor: 56.272

6.  Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.

Authors:  Ian P M Tomlinson; N Afrina Alam; Andrew J Rowan; Ella Barclay; Emma E M Jaeger; David Kelsell; Irene Leigh; Patricia Gorman; Hanan Lamlum; Shamima Rahman; Rebecca R Roylance; Simon Olpin; Stephen Bevan; Karen Barker; Nicholas Hearle; Richard S Houlston; Maija Kiuru; Rainer Lehtonen; Auli Karhu; Susa Vilkki; Päivi Laiho; Carita Eklund; Outi Vierimaa; Kristiina Aittomäki; Marja Hietala; Pertti Sistonen; Anders Paetau; Reijo Salovaara; Riitta Herva; Virpi Launonen; Lauri A Aaltonen
Journal:  Nat Genet       Date:  2002-02-25       Impact factor: 38.330

7.  Fumarate hydratase deficient renal cell carcinoma: Chromosomal numerical aberration analysis of 12 cases.

Authors:  Kristyna Pivovarcikova; Petr Martinek; Petr Grossmann; Kiril Trpkov; Reza Alaghehbandan; Cristina Magi-Galluzzi; Maria Pane Foix; Enric Condom Mundo; Daniel Berney; Anthony Gill; Boris Rychly; Kvetoslava Michalova; Joanna Rogala; Tomas Pitra; Tamas Micsik; Jiri Polivka; Milan Hora; Ozlem Tanas Isikci; Sarka Skalova; Jana Mareckova; Michal Michal; Ondrej Hes
Journal:  Ann Diagn Pathol       Date:  2019-02-10       Impact factor: 2.090

8.  Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer.

Authors:  Brian Shuch; Shantao Li; Harvey Risch; Ranjit S Bindra; Patrick D McGillivray; Mark Gerstein
Journal:  Cancer       Date:  2020-05-15       Impact factor: 6.860

9.  Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

Authors:  Robert J Motzer; Konstantin Penkov; John Haanen; Brian Rini; Laurence Albiges; Matthew T Campbell; Balaji Venugopal; Christian Kollmannsberger; Sylvie Negrier; Motohide Uemura; Jae L Lee; Aleksandr Vasiliev; Wilson H Miller; Howard Gurney; Manuela Schmidinger; James Larkin; Michael B Atkins; Jens Bedke; Boris Alekseev; Jing Wang; Mariangela Mariani; Paul B Robbins; Aleksander Chudnovsky; Camilla Fowst; Subramanian Hariharan; Bo Huang; Alessandra di Pietro; Toni K Choueiri
Journal:  N Engl J Med       Date:  2019-02-16       Impact factor: 91.245

10.  Everolimus plus bevacizumab is an effective first-line treatment for patients with advanced papillary variant renal cell carcinoma: Final results from a phase II trial.

Authors:  Darren R Feldman; Yasser Ged; Chung-Han Lee; Andrea Knezevic; Ana M Molina; Ying-Bei Chen; Joshua Chaim; Devyn T Coskey; Samuel Murray; Satish K Tickoo; Victor E Reuter; Sujata Patil; Han Xiao; Jahan Aghalar; Arlyn J Apollo; Maria I Carlo; Robert J Motzer; Martin H Voss
Journal:  Cancer       Date:  2020-09-25       Impact factor: 6.860
View more
  7 in total

1.  Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates.

Authors:  Chung-Han Lee; Martin H Voss; Maria Isabel Carlo; Ying-Bei Chen; Mark Zucker; Andrea Knezevic; Robert A Lefkowitz; Natalie Shapnik; Chloe Dadoun; Ed Reznik; Neil J Shah; Colette Ngozi Owens; Deaglan Joseph McHugh; David Henry Aggen; Andrew Leonard Laccetti; Ritesh Kotecha; Darren R Feldman; Robert J Motzer
Journal:  J Clin Oncol       Date:  2022-03-17       Impact factor: 50.717

2.  Genomic and Metabolic Hallmarks of SDH- and FH-deficient Renal Cell Carcinomas.

Authors:  Angela Yoo; Cerise Tang; Mark Zucker; Kelly Fitzgerald; Renzo G DiNatale; Phillip M Rappold; Kate Weiss; Benjamin Freeman; Chung-Han Lee; Nikolaus Schultz; Robert Motzer; Paul Russo; Jonathan Coleman; Victor E Reuter; Ying-Bei Chen; Maria I Carlo; Anthony J Gill; Ritesh R Kotecha; A Ari Hakimi; Ed Reznik
Journal:  Eur Urol Focus       Date:  2022-03-11

3.  Characterization of FH-deficient renal cell carcinoma.

Authors:  Louise Stone
Journal:  Nat Rev Urol       Date:  2021-05       Impact factor: 14.432

Review 4.  [FH-deficient renal cell carcinoma expands the spectrum of renal papillary tumors].

Authors:  N Rupp; H Moch
Journal:  Pathologe       Date:  2021-08-27       Impact factor: 1.011

Review 5.  Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma.

Authors:  Andrea Katharina Lindner; Gennadi Tulchiner; Andreas Seeber; Peter J Siska; Martin Thurnher; Renate Pichler
Journal:  Front Oncol       Date:  2022-07-15       Impact factor: 5.738

6.  Fumarate hydratase-deficient renal cell carcinoma in extended remission with bevacizumab and erlotinib.

Authors:  Shubham Tomar; Lakhan Kashyap; Akhil Kapoor
Journal:  Ecancermedicalscience       Date:  2022-05-30

Review 7.  Papillary renal cell carcinoma: current and controversial issues.

Authors:  Silvia Angori; João Lobo; Holger Moch
Journal:  Curr Opin Urol       Date:  2022-06-09       Impact factor: 2.808
  7 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.