Molecular Pathogenesis in Sporadic Head and Neck Paraganglioma

Abstract

Hypothesis: Similar to familial tumors, sporadic head and neck paragangliomas are associated with chromosomal deletions at either 11q13 or 11q22-23. Background: Familial paragangliomas are inherited in an autosomal dominant pattern with genomic imprinting of the maternal allele. Genetic studies of familial paragangliomas have localized the causative genetic defect to two separate loci: 11q13.1 and 11q22-23. The molecular pathogenesis of sporadic head and neck paragangliomas has not been studied. Methods: Blood and tumor samples from patients with sporadic head and neck paragangliomas were screened for deletions on chromosome 11 using DNA microsatellite markers and polymerase chain reaction. Polymerase chain reaction-amplified alleles from tumor specimens were compared with those from the blood of eight patients. A greater than 50% reduction in band intensity (as determined by densitometric analysis) between blood and tumor sample was indicative of a chromosomal deletion. Results: Three of the eight patients were found to have deletions at chromosome 11q: two at chromosome 11q22-23 and one at 11q13. Conclusions: Sporadic head and neck paragangliomas are associated with deletions at chromosome 11q13 and 11q22-23. It is thus likely that sporadic and familial paragangliomas share a similar molecular pathogenesis.

Mouse Models of Human Familial Paraganglioma

“…Sdh gene defects may also be the cause of sporadic head and neck PGLs where deletions at the same or closely related loci (11q13 and 11q22-23) are observed (Bikhazi et al, 2000). The remaining half of familial PGLs result from inherited mutations associated with von Hippel-Lindau (VHL) syndrome, multiple endocrine neoplasia type 2 (MEN 2), or neurofibromatosis genes (Inabnet et al, 2000;Bryant et al, 2003).…”

Head and Neck Paraganglioma: Medical Assessment, Management, and Literature Update

“…HNPGL are rare and represent 0.03% of human tumours and 0.6% of head and neck tumours, having an estimated incidence of one in 30,000 [13,14]. Malignancy in HNPGL is extremely rare occurring in 1-3% of lesions [15]; there were no patients with malignant progression in our series.…”

Progressive Facial Paralysis Secondary to a Rare Temporal Bone Tumor<subtitle>Glomus Faciale</subtitle>

“…Genetic studies of sporadic tumors in the head and neck have localized deletion defects at the 11q13 and 11q22-23 loci, possibly linking the molecular pathogenesis of both familial and sporadic types. 14 While most tumors are solitary, multiple tumors are seen in patients with multiple endocrine neoplasia types 2a and 2b characterized by mutations in the RET proto-oncogene, among other less commonly associated disorders such as neurofibromatosis and von Hippel-Lindau disease. Familial predisposition occurs in approximately 10% to 50%.…”