Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors

被引：100

作者：

Rodrigues, Manuel ^{[1
,2
]}

Mobuchon, Lenha ^{[1
]}

Houy, Alexandre ^{[1
]}

Fievet, Alice ^{[1
,3
]}

Gardrat, Sophie ^{[4
]}

Barnhill, Raymond L. ^{[4
,5
]}

Popova, Tatiana ^{[1
]}

Servois, Vincent ^{[6
]}

Rampanou, Aurore ^{[7
]}

Mouton, Aurore ^{[8
]}

Dayot, Stephane ^{[1
]}

Raynal, Virginie ^{[9
,10
]}

Galut, Michele ^{[11
]}

Putterman, Marc ^{[12
]}

Tick, Sarah ^{[13
]}

Cassoux, Nathalie ^{[5
,14
]}

Roman-Roman, Sergio ^{[15
]}

Bidard, Francois-Clement ^{[2
,7
,16
]}

Lantz, Olivier ^{[8
]}

Mariani, Pascale ^{[17
]}

Piperno-Neumann, Sophie ^{[2
]}

Stern, Marc-Henri ^{[1
,3
]}

机构：

[1] PSL Res Univ, Inst Curie, INSERM U830, DRUM,Equipe Labellisee Ligue Natl Canc, F-75248 Paris, France

[2] PSL Res Univ, Inst Curie, Dept Med Oncol, F-75248 Paris, France

[3] PSL Res Univ, Inst Curie, Dept Genet, F-75248 Paris, France

[4] PSL Res Univ, Inst Curie, Dept Biopathol, F-75248 Paris, France

[5] Univ Paris 05, Fac Med, F-75006 Paris, France

[6] PSL Res Univ, Inst Curie, Dept Med Imaging, F-75248 Paris, France

[7] PSL Res Univ, Inst Curie, Lab Circulating Tumor Biomarkers, SiRIC, F-75248 Paris, France

[8] PSL Res Univ, Inst Curie, INSERM CIC BT 1428, F-75248 Paris, France

[9] PSL Res Univ, Inst Curie, INSERM U830, F-75248 Paris, France

[10] Inst Curie Genom Excellence ICGex Platform, F-75248 Paris, France

[11] PSL Res Univ, Inst Curie, Biol Resource Ctr, F-75248 Paris, France

[12] Quinze Vingts Natl Ophthalmol Hosp, Dept Pathol, F-75012 Paris, France

[13] Quinze Vingts Natl Ophthalmol Hosp, Dept Ophthalmol 3, F-75012 Paris, France

[14] PSL Res Univ, Inst Curie, Dept Ocular Oncol, F-75248 Paris, France

[15] PSL Res Univ, Inst Curie, Dept Translat Res, F-75248 Paris, France

[16] Paris Saclay Univ, UVSQ, F-78035 St Quentin en Yvelines, France

[17] PSL Res Univ, Inst Curie, Dept Surg Oncol, F-75248 Paris, France

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

CANCER; DNA; IDENTIFICATION; BLOCKADE; DATABASE; CELLS; PD-1;

D O I：

10.1038/s41467-018-04322-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactivation in the tumor. We identify additional tumors in The Cancer Genome Atlas (TCGA) cohorts with similar hypermutator profiles in patients carrying germline deleterious MBD4 mutations and somatic loss of heterozygosity. This MBD4-related hypermutator phenotype may explain unexpected responses to immune checkpoint inhibitors.

引用

页数：6

共 50 条

[41] CT texture analysis as a predictor of favorable response to anti-PD1 monoclonal antibodies in metastatic skin melanoma
Bonnin, Angele
Durot, Carole
Barat, Maxime
Djelouah, Manel
Grange, Florent
Mule, Sebastien
Soyer, Philippe
Hoeffel, Christine
DIAGNOSTIC AND INTERVENTIONAL IMAGING, 2022, 103 (02) : 97 - 102
[42] Pre-treatment DNA methylome and transcriptome profiles correlate with melanoma response to anti-PD1 immunotherapy
Hossain, Sultana Mehbuba
Gimenez, Gregory
Stockwell, Peter
Weeks, Robert
Almomani, Suzan
Jones, Gregory T.
Ratajska, Magdalena
Shuen, Mathew
Bhat, Basharat
Rys, Janusz
Cybulska-Stopa, Bozena
Harazin-Lechowska, Agnieszka
Rodger, Euan
Jackson, Christopher
Chatterjee, Aniruddha
Eccles, Michael R.
CANCER LETTERS, 2025, 618
[43] Anti-PD1 Following Ipilimumab for Mucosal Melanoma: Durable Tumor Response Associated with Severe Hypothyroidism and Rhabdomyolysis
Min, Le
Hodi, F. Stephen
CANCER IMMUNOLOGY RESEARCH, 2014, 2 (01) : 15 - 18
[44] Immunomodulating antibodies in the treatment of metastatic melanoma: The experience with anti-CTLA-4, anti-CD137, and anti-PD1
Simeone, Ester
Ascierto, Paolo A.
JOURNAL OF IMMUNOTOXICOLOGY, 2012, 9 (03) : 241 - 247
[45] Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma
Sam, Ikuan
Benhamouda, Nadine
Biard, Lucie
Da Meda, Laetitia
Desseaux, Kristell
Baroudjan, Barouyr
Nakouri, Ines
Renaud, Marion
Sadoux, Aurelie
Alkatrib, Marina
Deleuze, Jean-Francois
Battistella, Maxime
Shen, Yimin
Resche-Rigon, Matthieu
Mourah, Samia
Lebbe, Celeste
Tartour, Eric
EMBO MOLECULAR MEDICINE, 2025,
[46] Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy
Rose, April A. N.
Armstrong, Susan M.
Hogg, David
Butler, Marcus O.
Saibil, Samuel D.
Arteaga, Diana P.
Muniz, Thiago Pimentel
Kelly, Deirdre
Ghazarian, Danny
King, Ian
Kamil, Zaid Saeed
Ross, Kendra
Spreafico, Anna
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2021, 9 (01)
[47] Effect of radiofrequency ablation (RFA) combined with anti-CTLA-4 and anti-PD1 in a preclinical melanoma model.
Franco-Mahecha, Olga L.
Christou, Anna
Mauda-Havakuk, Michal
Katti, Prateek
Pritchard, William F.
Karanian, John W.
Wood, Bradford J.
JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (08)
[48] Early memory differentiation and cell death resistance in T cells predicts melanoma response to sequential anti-CTLA4 and anti-PD1 immunotherapy
Isaure Vanmeerbeek
Daniel M. Borras
Jenny Sprooten
Oliver Bechter
Sabine Tejpar
Abhishek D. Garg
Genes & Immunity, 2021, 22 : 108 - 119
[49] Early memory differentiation and cell death resistance in T cells predicts melanoma response to sequential anti-CTLA4 and anti-PD1 immunotherapy
Vanmeerbeek, Isaure
Borras, Daniel M.
Sprooten, Jenny
Bechter, Oliver
Tejpar, Sabine
Garg, Abhishek D.
GENES AND IMMUNITY, 2021, 22 (02) : 108 - 119
[50] The relationship between BRAF/NRAS/KIT genomic driver mutations and anti-PD1 immunotherapy responses in patients with advanced melanoma
Rose, April A. N.
Armstrong, Susan M.
Hogg, David
Butler, Marcus
Joshua, Anthony M.
Ghazarian, Danny
Kamel-Reid, Suzanne
Al Habeeb, Ayman
Chappell, Mary Anne
Ross, Kendra
Amir, Eitan
Bedard, Phillippe L.
Siu, Lillian
Spreafico, Anna
CANCER RESEARCH, 2019, 79 (13)

← 1 2 3 4 5 →