Abstract
Introduction
Chordoma is the most common primary spinal tumor with a median survival of 6 to 7 years, with high recurrence rates. Radical surgical resection remains the mainstay of treatment, with radiation often utilized to enhance local disease control. There are no approved chemotherapeutic agents for chordomas. Brachyury, coded by the T gene, has been implicated in the pathogenesis of chordomas and is highly expressed in most of these tumors. Recently, Pillay et al found that the single nucleotide polymorphism (SNP) rs2305089 in the T gene was associated with chordoma development. The variant A allele at rs2305089 results in a p.Gy177Asp change in Brachyury. Given the rarity of this disease, with an incidence of 0.08 per 100,000 individuals, determining the clinical significance of this SNP has been challenging.
Materials and Methods
This study included both prospective and retrospective data collected from five high-volume centers within Europe and North America. Data were collected between 1990 and 2013, through the AOSpine Knowledge Forum Tumor (AOSKFT) primary tumor database. Institutional approval was obtained before studying the tumor samples.
Results
In the overall cohort of 109 patients, survival at last follow-up (mean follow-up: 1,330 ± 1,475 days) was 69.7%. Seven (6.4%) patients had the GG genotype, while 66 (60.6%) and 36 (33.3%) patients had the AA and GA genotypes, respectively. In the 102 cases with the A variant, 75 (73.5%) were alive at the last follow-up compared with only 1 (14.3%) of the 7 patients with the GG genotype. Local recurrence rates were similar between the populations with the A variant and those without, with 40 (39.2%) patients with the A variant experiencing local recurrence compared with 2 (33.3%) patients without the A variant.
Conclusions
There is a trend toward worse survival in individuals with the GG genotype than with the AA or GA genotypes. To our knowledge, this is the first time the rs2305089 SNP has been considered in the prognosis and survival of individuals with chordoma.