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Sarcomatoid Renal Cell Carcinoma Has a Distinct Molecular Pathogenesis, Driver Mutation Profile, and Transcriptional

Zixing Wang1, Tae Beom Kim1, Bo Peng1

  • 1Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 16, 2017
PubMed

Insights

Sarcomatoid renal cell carcinoma (SRCC) is aggressive and molecularly distinct from other renal cell carcinomas (RCC). Sarcomatoid clear-cell RCC (SccRCC) has a unique molecular origin, impacting diagnosis and prognosis.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Pathology

Background:

  • Sarcomatoid renal cell carcinoma (SRCC) is an aggressive subtype of renal cell carcinoma (RCC).
  • Limited genome-wide molecular data exists for SRCC, hindering understanding of its pathogenesis.
  • SRCC exhibits diverse clinicopathologic features and aggressive behavior.

Purpose of the Study:

  • To perform comprehensive molecular profiling of SRCC.
  • To compare molecular characteristics of SRCC with non-sarcomatoid RCC (RCC).
  • To elucidate the distinct molecular drivers and pathways in SRCC subtypes.

Main Methods:

  • Whole-exome sequencing, SNP arrays, and RNA sequencing were employed.
  • Data from 65 SRCC and 598 RCC patients were analyzed.
  • Molecular data were compared across parent RCC subtypes (clear-cell, papillary, chromophobe).

Main Results:

  • SRCC molecularly segregated by parent RCC subtype but showed TGFβ pathway upregulation.
  • Sarcomatoid clear-cell RCC (SccRCC) lacked typical 3p21-25 deletions and VHL/PBRM1 alterations seen in clear-cell RCC.
  • SccRCC exhibited distinct mutations in PTEN, TP53, and RELN, associated with worse prognosis compared to VHL alterations.

Conclusions:

  • SRCC subtypes are molecularly distinct, with SccRCC having a unique early molecular pathogenesis.
  • The findings support a more precise molecular classification of RCC.
  • These molecular differences have significant diagnostic, prognostic, and therapeutic implications.

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