Abstract
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an extremely rare syndrome with autosomal dominant inheritance. HLRCC is characterized by a predisposition to leiomyomas of the skin and the uterus as well as renal cell carcinoma. The disease-related gene has been identified as fumarate hydratase (fumarase, FH), which encodes an enzyme involved in the mitochondrial tricarboxylic acid cycle. Protein profiling may give some insight into the molecular pathways of HLRCC. Therefore, we performed protein profiling of blood samples from HLRCC patients, their family members, and healthy volunteers, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) coupled with IMAC-Cu chips. For hierarchical clustering analysis, we used the 45 peaks that revealed significant differences in single-marker analysis over the range from 1500 to 15,000 m/z. Heat map analysis based on the results of clustering distinguished the HLRCC kindred from non-HLRCC subjects with a sensitivity of 94% and a specificity of 90%. SELDI-TOF MS profiling of blood samples can be applied to identify patients with HLRCC and to assess specific molecular mechanisms involved in this condition.
Highlights
Hereditary leiomyomatosis and renal cell cancer (HLRCC, Online Mendelian Inheritance in Man accession number 605839) is a recently identified autosomal dominant tumor susceptibility syndrome characterized by a predisposition for the development of benign leiomyomas of the skin and the uterus, as well as aggressive renal cell carcinoma with papillary type 2 or collecting duct histology [1,2,3,4]
We examined serum samples from a Japanese HLRCC kindred by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and attempted to discriminate them from samples provided by healthy controls
We found that quantitative mass spectrometry could be applied to identify patients with HLRCC
Summary
Hereditary leiomyomatosis and renal cell cancer (HLRCC, Online Mendelian Inheritance in Man accession number 605839) is a recently identified autosomal dominant tumor susceptibility syndrome characterized by a predisposition for the development of benign leiomyomas of the skin and the uterus (fibroids and myomas), as well as aggressive renal cell carcinoma with papillary type 2 or collecting duct histology [1,2,3,4]. In HLRCC, there is a germline mutation and subsequent somatic loss of the second allele results in tumorigenesis. It appears that other genetic or environmental factors might be involved in causing an increase of susceptibility to renal cancer in addition to FH mutation [6]
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