Frequency of loss of heterozygosity of the NF2 gene in schwannomas from Croatian patients

Abstract

Aim: To identify gross deletions in the NF2 gene in a panel of schwannomas from Croatian patients in order to establish their frequencies in Croatian population.

Methods: Changes of the NF2 gene were tested by polymerase chain reaction/loss of heterozygosity (LOH) using two microsatellite markers, D22S444 and D22S929.

Results: The analysis with both markers demonstrated that 43.75% of schwannomas exhibited LOH of the NF2 gene. The D22S444 region exhibited 45.5% of LOHs and the D22S929 region exhibited 14.3% of LOHs. Four LOHs were found in Antoni B, 2 in Antoni A, and 1 in Antoni A and B type tumors.

Conclusion: The frequency of changes observed in Croatian patients is broadly similar to that reported in other populations and thus confirms the existing hypothesis regarding the tumorigenesis of schwannomas and contributes to schwannoma genetic profile helping us to better understand its etiology and treatment.

Figure 1

Vestibular schwannoma, (A) Antoni A. Tumors were composed of compact spindle cells that had twisted nuclei and indistinct cytoplasmic borders. They were arranged in short bundles. Nuclear palisading and Verocay bodies were present. (B) Antoni B. The tumor was composed of loosely arranged Schwann cells admixed with foamy macrophages. In some tumor cells degenerative nuclear changes were seen but mitotic activity was not observed (200 × , hematoxylin and eosin).

Figure 2

Magnetic resonance image showing lesion in the left pontocerebellar angle.

Figure 3

Losses of heterozigosity (LOHs) of the NF2 gene in schwannomas. (A) Lanes 1, 3, 6 – samples demonstrating LOH at D22S444; lanes 2, 4, 5 –corresponding blood samples; lanes 7, 8 – uninformative patient. (B) Lane 1 –100 bp DNA standard; lanes 5, 7, 11 –samples demonstrating LOH at D22S929; lanes 4, 6, 10 – corresponding blood samples; lanes 2, 3 – heterozygous patient without LOH; lanes 8, 9 – uninformative patient.