Clinical and Translational Oncology

, Volume 10, Issue 11, pp 697–712

Origin of renal cell carcinomas

  • Manuel Valladares Ayerbes
  • Guadalupe Aparicio Gallego
  • Silvia Díaz Prado
  • Paula Jiménez Fonseca
  • Rosario García Campelo
  • Luis Miguel Antón Aparicio
Educational Series


Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the “two hits” of Knudson’s hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition.


Stem cell Stem cell markers Bone marrow stem cells 


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Copyright information

© Feseo 2008

Authors and Affiliations

  • Manuel Valladares Ayerbes
    • 1
  • Guadalupe Aparicio Gallego
    • 2
  • Silvia Díaz Prado
    • 2
    • 3
  • Paula Jiménez Fonseca
    • 4
  • Rosario García Campelo
    • 1
  • Luis Miguel Antón Aparicio
    • 1
    • 3
  1. 1.Medical Oncology ServiceCHU Juan Canalejo Materno Infantil HospitalA CoruñaSpain
  2. 2.Investigation & Oncology Research UnitCHU Juan CanalejoLa CoruñaSpain
  3. 3.Department of MedicineUniversity of La CoruñaLa CoruñaSpain
  4. 4.Medical Oncology ServiceCentral HospitalAsturiasSpain

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