Markers for Early Diagnosis of Cancer

Topics in This Section

Developed by:

  • Margie L. Clapper, PhD

  • Alfonso Bellacosa, MD, PhD

  • Background:

    The technology is based on two diseases linked with propensity to renal cancer: TSC (tuberous sclerosis complex) and (VHL) von Hippel-Lindau syndromes, which are tumor suppressor gene disorders of TSC1, TSC2, and VHL, respectively. TSC1 (hamartin) and TSC2 (tuberin) physically collaborate and are involved in many cellular events. TSC is characterized by seizures, mental retardation, and cancer of numerous tissues. VHL consists of abnormal blood vessel growth, known as hemangioblastomas or angiomas. The negative regulation of the HIF1 transcription factor by TSC and VHL controls cell signaling and growth. Therefore, alteration of TSC or VHL can lead to tumorigenesis, especially in the kidney. Previously, it was postulated that cells heterozygous for a mutant tumor suppressor gene would exhibit no substantial traits to distinguish them from normal cells. However, cDNA microarray analysis and RT-PCR of patients heterozygous for TSC or VHL led to classification of significant gene expression changes, including genes formerly found in homozygous mutant tumor cells, thus validating this novel approach. Importantly, the single gene modifications seen in TSC1, TSC2, and VHL correlate with the initial stages of kidney cancer.

    Summary Invention:

    Dr. Alfred Knudson, Dr. Margie Clapper, and Dr. Alfonso Bellacosa, their colleagues at Fox Chase Cancer Center, and the National Cancer Institute have employed a technique for the evaluation of phenotypically normal tissues from patients heterozygous for altered genes that correlate with cancer development. They have used this technique to identify renal cancer markers.


    Although data and analysis were originally performed with regard to TSC and VHL genes that correlate with renal cancer, the discovery can be applied to any cancers involving tumor suppressor genes, such as APC and mismatch repair genes (involved in colon cancer), BRCA1, BRAC2 (involved in breast, ovarian, and prostate cancer, as well as BRCA2 carriers at risk for pancreatic cancer), EXT1 and EXT2 (involved in cartilage cancer), and DPC4 and CDKN2 (involved in pancreatic cancer). At present, markers for breast, ovarian, and colon cancers are being investigated. These "single hit" gene alterations seem to be indications of early molecular developments for cancer progression, and their distinctive characteristics can serve as tools for early cancer diagnosis, prevention, treatment, and prognosis. In addition, the discovery is relevant not only for heterozygous mutant patients, but also for the common sporadic, non-hereditary cases since the latter have often somatic mutations in the same genes.

    Patent Status:

    A U.S. provisional patent application has been filed covering the method of characterizing genetic markers of kidney, breast, ovarian, and colon cancers, and the genetic markers themselves.

    For licensing information, contact

    Inna Khartchenko, MS, MBA
    Director, Licensing
    Associate Director, Office of Corporate Alliances Fox Chase Cancer Center
    610 Old York Road, Suite 400
    Room 409
    Jenkintown, PA 19046
    Tel.: 215-214-3989
    Fax: 215-214-1440