Trial Information

Analysis of NF2 Mutations in Radiation-Related Neural Tumors

Adults treated with X-rays in childhood for benign conditions such as enlarged tonsils and
adenoids have an increased risk of developing nervous system tumors. The risk is highest
for schwannomas (RR of 33.1, 95% CI of 9.4-116.5), intermediate for meningiomas (RR of 9.5,
95% CI of 3.5-25.7) and lowest for gliomas (RR of 2.6, 95% CI of 0.8-8.6).

Studies of sporadic tumors of these types have demonstrated the presence of somatic
mutations in the NF2 gene. Because these mutations are not usually seen in other types of
tumors, they are believed to be what caused the sporadic neural tumors to develop. Germline
mutations in the same gene are responsible for the autosomal dominant disorder known as
neurofibromatosis 2 (NF2) which is characterized by the development of similar types of
neural tumors.

The purpose of the proposed study is to determine if neural tumors that developed in people
who were treated with X-rays in childhood also have somatic NF2 mutations. This will be
done using DNA from paraffin-embedded neural tumors that developed in ~ 112 individuals
treated with X-rays in childhood for benign head and neck conditions. These individuals are
from a cohort of over 4,000 irradiated persons followed by Michael Reese Hospital in
Chicago since 1974. If we find NF2 mutations in the radiation-related tumors, we will
determine whether they are somatic or germline by looking for NF2 mutations in DNA from
buccal cells of the patients with the studied tumors. We expect that most patients will
have NF2 mutations only in tumor DNA. However, there is a remote possibility that one or
more patients may have a germline NF2 mutation and thus an increased risk of developing
neural tumors even in the absence of X-ray treatment. We will then compare the types and
frequencies of the somatic NF2 mutations with those found in sporadic neural tumors. If we
do not find somatic NF2 mutations in the radiation-related tumors, we will conclude that
X-rays caused neural tumors to develop through interactions with another gene or genes.
Either result will contribute to our knowledge of radiation tumorigenesis.

We will send letters describing this study to patients from the Michael Reese Hospital
cohort who have developed radiation-related neural tumors. Those who consent to take part
in it will be asked for permission to obtain paraffin blocks from any neural tumor that they
have had removed and to donate buccal cells for NF2 mutation studies. Finally, they will
also be asked to complete a questionnaire that will help us update their medical history and
obtain a medical history on close blood relatives.