INHERIT EGFR - Studying Germline EGFR Mutations

If a subject have lung cancer or another cancer carrying a T790M mutation in the EGFR gene,
he/she may be eligible to participate in this research study. To determine eligibility, a
subject will need to perform the following steps: provide informed consent, fill out the
study questionnaire and provide medical records documentation.

The study questionnaire should take about 30 minutes to complete. The questionnaire asks for
information on personal and family cancer and health history. The information provided will
help investigators to determine which parts of the study a subject is eligible for. A few
weeks after submitting the questionnaire, a member of the research study team will contact
the subject by telephone to clarify any questions about the response.

For medical records documentation investigators will request permission to obtain and review
medical records pertaining to any personal history of cancer. Subjects will need to complete
a medical record release form to allow investigators to collect medical records regarding
prior cancers and cancer treatment.

After a subject is determined to be eligible, he/she will have a conversation with a genetic
counselor regarding the potential risks, benefits and limitations of genetic testing. A
genetic counselor is an expert in the field of inherited disorders. They work as members of
the health care team and act as a patient advocate providing education and support to the
patient, family and the medical team. If a subject agrees to proceed, he/she will be provided
a kit (by mail or in person) to provide a saliva sample for genetic testing. This involves
spitting into a special container provided by the study. This sample will be sent to a
clinically-certified testing laboratory to determine presence of an inherited EGFR mutation.

Once the results have been determined, the subject will receive a letter with the phone
number of a genetic counselor to call in order to review results of the genetic testing.
Alternatively, a subject can decide not to receive the results of the genetic testing and can
note that on the letter received and send it back to the study team instead of calling for
the results.

If a mutation is found in the saliva sample, a subject will receive information about how to
undergo confirmatory testing of a blood specimen. This can be done at a local laboratory
using a kit that will be mailed. When the results are available a genetic counselor will call
to discuss them. If the confirmatory blood test confirms an inherited mutation, subjects will
receive instructions on how to invite family members to be tested if appropriate.

Investigators will collect material from a prior tumor biopsy (if available), copies of
imaging scans, and medical records to study. The copies of imaging scans will allow study of
the characteristics of nodules in the lungs. This information will be used to answer
additional questions about cancers carrying EGFR T790M mutations.

It will only take a few months to complete the main part of the study. After that, subjects
will be followed every 6 months for 2 years. If a subject allows a piece of a tumor specimen
or DNA to be stored for future investigational studies, then he/she will remain enrolled in
research for as long as the specimen is stored in the specimen bank.

Inclusion Criteria:

To participate in this study a subject must meet the eligibility of one of the following
cohorts:

Cohort 1 - Cancer patients with T790M in their tumor must both:

- Have a diagnosis of cancer of any type (lung cancer or other)

- Have an EGFR mutation identified. Either EGFR T790M identified on tumor genotyping of
their cancer OR on quantitative plasma genotyping with evidence of high level (>40%
allelic fraction) EGFR T790M OR

- Another EGFR mutation previously reported as germline detected on tumor genotyping of
their cancer

Cohort 2 - Relatives of carriers of germline EGFR mutations are eligible as follows:

- First-degree or second-degree relatives of an individual known to carry a germline
EGFR mutation (either T790M or other novel germline EGFR mutation)

- Third-degree relatives of an individual known to carry a germline EGFR mutation
(either T790M or other novel germline EGFR mutation) if the relative has a personal
history of lung cancer or another malignancy

Cohort 3 - Individuals already known to carry a germline EGFR mutation must:

- Have a known germline EGFR mutation (either T790M or other novel germline EGFR
mutation)

Exclusion Criteria:

- Subjects with lung cancer and an acquired T790M mutation first detected after exposure
to an EGFR tyrosine kinase inhibitor such as erlotinib or gefitinib

- Subjects who are too ill to complete the study questionnaire or provide the necessary
specimen for testing

- Subjects who are unable to give informed consent

- Subjects who are unable to speak or read English or Brazilian Portuguese

- Subjects under the age of 18