Related Experiment Video

Updated: Sep 18, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.2K

Renal Tumorigenesis via RAS/RAF/MAPK Pathway Alterations Beyond Papillary Renal Neoplasm With Reverse Polarity

Jung Woo Kwon1, Peng Wang, Pankhuri Wanjari

  • 1Department of Pathology, The University of Chicago, Chicago, IL.

The American Journal of Surgical Pathology
|June 25, 2025
PubMed

Insights

RAS/RAF/MAPK pathway alterations are identified in rare renal tumors, presenting diverse molecular and morphological features. Recognizing these alterations is crucial for potential targeted therapies in kidney cancer.

Area of Science:

  • Oncology
  • Genetics
  • Pathology

Background:

  • The RAS/RAF/MAPK signaling pathway is well-defined in cancer, but its role in renal tumorigenesis is largely unknown.
  • Papillary renal neoplasm with reverse polarity (PRNRP) is an exception, known to harbor KRAS alterations.

Purpose of the Study:

  • To investigate the role and characteristics of RAS/RAF/MAPK pathway alterations in renal tumors.
  • To explore the morphological, immunohistochemical, and molecular heterogeneity of these tumors.

Main Methods:

  • Next-generation sequencing (NGS) was performed on 383 renal tumors from the University of Chicago and 406 tumors from TCGA PRCC/chromophobe RCC datasets.
  • Tumors with RAS/RAF/MAPK pathway alterations were identified and classified into three groups based on morphology.

Main Results:

  • Fifteen renal tumors with RAS/RAF/MAPK pathway alterations were identified (KRAS, BRAF, RAF1, NRAS).
  • Three distinct morphological groups emerged: classic PRNRPs, predominantly tubulocystic, and papillary with high-grade features.
  • High-grade papillary tumors (Group 3) showed more frequent additional genetic alterations, significant copy number variations, and metastatic potential, unlike low-grade groups.

Conclusions:

  • Renal tumors with RAS/RAF/MAPK pathway alterations are heterogeneous, exhibiting diverse morphological, immunohistochemical, and molecular profiles.
  • Identification of these alterations is clinically significant, offering potential targets for FDA-approved therapies.
Keywords:
RAS/RAF/MAPK pathwaypapillary renal neoplasm with reverse polarityrenal tumorigenesis

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