homozygous genotype and chromosome instability are associated with recurrence in adult granulosa cell tumors of the ovary.

INTRODUCTION

Adult granulosa cell tumors (aGCTs) are extremely rare tumors characterized by the presence of the single missense mutation (c.402 C>G, p. C134W) in the gene. These tumors are frequently associated with a slow, indolent disease progression and a high probability of aggressive tumor recurrence. Hence, the identification of molecular markers that are predictive of recurrence and/or aggressive behavior would be a great asset in the management of aGCT. The present study focused on the influence of the genotype (heterozygous or homozygous) and copy number variations (CNVs) in recurrence by comparing the primary tumor with recurrent lesions in the same patient. We performed array comparative genomic hybridization (CGH) experiments and genotyping by allelic discrimination on 40 tumor samples.

RESULTS AND DISCUSSION

In array CGH results of recurrent tumors, few samples presented the multiple chromosome losses and gains characteristic of chromosome instability (CIN). We also observed that three recurrent tumors and one primary tumor appeared to be homozygous for the c.402C>G mutation. Interestingly, the homozygous genotype was correlated with a shorter time to relapse. A change in the genotype in cases of recurrence was correlated with the appearance of CIN.

CONCLUSION

Despite the small number of matching primary and recurrent tumors analyzed here, the present study is the first to have shown that the homozygous genotype and CIN are prevalent in recurrent aGCTs. The two mechanisms are probably linked, and both almost certainly have a role in the molecular transformation of aGCTs.