Login to Access Video or Poster Abstract: MP67-01
Sources of Funding: Supported by National Natural Science Foundation of China(Grand number 81572506)

Introduction

von Hipple-Lindau(VHL) disease is an autosomal dominant familial cancer syndrome with a birth incidence of around 1/36000. Renal cell carcinoma(RCC) occurs in 35% of VHL patients, and is one of the main death causes. In order to describe the genetic characteristics of Chinese VHL patients, we have evaluated the telomere length and genetic anticipation in a large cohort of Chinese von Hipple-Lindau disease.

Methods

We recruited 140 patients from 70 families with VHL disease and 51 normal controls. Onset age was defined as the age when any symptom or sign of VHL disease first appeared. Genomic DNA was extracted from peripheral blood and age-adjusted relative telomere length(aRTL) was measured with qRT-PCR method. 101 parent-child pairs were analysed for genetic anticipation by paired t test.

Results

The mean onset age in our cohort was 29.5±11.6 years, and RCC occurred in 48.6%(68/140) VHL patients. Onset age was 16.8 years earlier for child than parent in the parent-child pairs(p<0.001). Patients in the next generation had younger onset age with shorter age-adjusted relative telomere length (p=0.018) in the 27 parent-child pairs. In addition, age-adjusted relative telomere length was shorter in the 140 VHL patients than in the normal controls(p=0.038).

Conclusions

This study provide evidence that telomere shortening is associated with genetic anticipation in a large Chinese cohort of VHL disease, suggesting that it might be a mechanism for pathogenesis of VHL-associated tumors.

Funding

Supported by National Natural Science Foundation of China(Grand number 81572506)