Comprehensive proteogenomic characterization of rare kidney tumors

Ginny Xiaohe Li(University of Michigan), Lijun Chen(Johns Hopkins University), Yi Hsiao(University of Michigan), Rahul Mannan(University of Michigan), Yuping Zhang(University of Michigan), Jie Luo(University of Michigan), Francesca Petralia(Icahn School of Medicine at Mount Sinai), Hanbyul Cho(University of Michigan), Noshad Hosseini(University of Michigan), Felipe da Veiga Leprevost(University of Michigan), Anna Calinawan(Icahn School of Medicine at Mount Sinai), Yize Li(James S. McDonnell Foundation), Shankara Anand(Broad Institute), Aniket Dagar(University of Michigan), Yifat Geffen(Broad Institute), Chandan Kumar‐Sinha(University of Michigan), Seema Chugh(University of Michigan), Anne Le(Johns Hopkins University), Sean Ponce(Johns Hopkins University), Shenghao Guo(Johns Hopkins University), Cissy Zhang(Johns Hopkins University), Michael Schnaubelt(Johns Hopkins University), Nataly Naser Al Deen(James S. McDonnell Foundation), Feng Chen(Washington University in St. Louis), Wagma Caravan(James S. McDonnell Foundation), Andrew Houston(James S. McDonnell Foundation), Alex Hopkins(University of Michigan), Chelsea J. Newton(Van Andel Institute), Xiaoming Wang(University of Michigan), Daniel A. Polasky(University of Michigan), Sarah E. Haynes(University of Michigan), Fengchao Yu(University of Michigan), Xiaojun Jing(University of Michigan), Siqi Chen(James S. McDonnell Foundation), Ana I. Robles(Cancer Clinic), Mehdi Mesri(Cancer Clinic), Mathangi Thiagarajan(Frederick National Laboratory for Cancer Research), Eunkyung An(Cancer Clinic), Gad Getz(Broad Institute), W. Marston Linehan(National Institutes of Health), Galen Hostetter(Van Andel Institute), Scott D. Jewell(Van Andel Institute), Daniel W. Chan(Johns Hopkins University), Pei Wang(Icahn School of Medicine at Mount Sinai), Gilbert S. Omenn(University of Michigan), Rohit Mehra(University of Michigan), Christopher J. Ricketts(National Institutes of Health), Li Ding(James S. McDonnell Foundation), Arul M. Chinnaiyan(Howard Hughes Medical Institute), Marcin Cieślik(University of Michigan), Saravana M. Dhanasekaran(University of Michigan), Hui Zhang(Johns Hopkins University), Alexey I. Nesvizhskii(University of Michigan), Alexander J. Lazar, Amanda G. Paulovich, Andrzej Antczak, Anthony R. Green, Avi Ma’ayan, Barb Pruetz, Bing Zhang(Johns Hopkins University), Boris Reva, Brian Druker, Charles A. Goldthwaite, Chet Birger, D.R. Mani(James S. McDonnell Foundation), David Chesla, David Fenyö, Eric E. Schadt, George D. Wilson, Iga Kołodziejczak(University of Michigan), Ivy John, Jason Hafron, Josh N. Vo(University of Michigan), Kakhaber Zaalishvili, Karen A. Ketchum, Karin Rodland, Kristen Nyce, Maciej Wiznerowicz, Marcin J. Domagalski, Meenakshi Anurag, Melissa Borucki, Michael A. Gillette(Johns Hopkins University), Michael J. Birrer, Nathan Edwards, Negin Vatanian, Pamela VanderKolk, Peter B. McGarvey, Rajiv Dhir, Ratna R. Thangudu, Reese Crispen, Richard Smith, Samuel Payne, Sandra Cottingham, Shuang Cai, Steven A. Carr, Tao Liu, Toan Le(University of Michigan), Weiping Ma(University of Michigan), Xu Zhang(Johns Hopkins University), Lu Yin(University of Michigan), Yvonne Shutack, Zhen Zhang(Johns Hopkins University)
Cell Reports Medicine
May 1, 2024
10.1016/j.xcrm.2024.101547
Cited by 44Open Access
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Abstract

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.

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