4th
FAMILIAL CANCER CONFERENCE - Madrid, Spain, June 7-8, 2010
BRCA2 Germline Mutation and risk of
ly mphoma
The inactivation of the pathway containing the BRCA1 and BRCA2 proteins would
increase the risk for lymphomas and leukemia. (Friedenson J. BMC Cancer 2007).
In people who do not have BRCA1 and BRCA2 gene mutations, the encoded
proteins prevent breast/ovarian cancer. However BRCA1 and BRCA2 proteins
have multiple functions including participating in a pathway that mediates repair of
DNA double strand breaks by error-free methods. Inactivation of “BRCA pathway”
due to a gene mutation should inactivate this error-free repair process. DNA
fragmets produced by double strand breaks are then left to non-specific processes
that rejoin them without regard for preserving normal gene regulation or function,
so rearrangements of DNA segments are more likely. These rearrangement are
typically associated with some lymphomas and leukemia. The evaluation of the
risks for cancer other than breast and ovarian in BRCA1-2 mutations carriers were
performed in only one case-control studies (Kadouri H. Med Genet 2007). In this
study the HR for lymphoma was 11.9 (95% CI 3.1 to 46.2%, p=0.001) in BRCA2
carriers. In 10% of our BRCA2 carriers patients (3/28 pts) we performed
lymphoma disease. In 17 mutated families we have 12 STOP-code-mutation with
premature interruption in protein synthesis. Two lymphoma cases arise in BC/OC
patients. In two patients we performed BRCA2’s breaking mutation (1466delT,
429Stop) and BRCA1’s unknown variant (3768T/C, Ser1217Leu).
BRCA1:
3768T/C, Ser1217Leu
BRCA2:
1466delT, 429Stop
+
Br40 Ex52
+
+
+
+
Ly 30 Br44
Br 39
+
Br Ex 39
Ly 30
Conclusions: The double alteration promotes the premature age of disease’s onset and
association of several tumors in the same patient. Our results suggest a role for BRCA2
mutations in lymphoma disease risk in a subgroup of BC/OC affected carriers. A correct
surveillance in the BRCA2 carriers patients BC/OC affected including physician
examination for the evaluation superficial lumpho-nodes status and the anamnesis for the
systemic symptoms.
Keywords: BRCA1, BRCA2, Lymphoma, Surveillance.
F . Ad a m i , F . C a r b o n a r d i , C . I r i d i l e ,
D.Zamagni, R.Cengarle,
S . V o l t o l i n i , G. C a v a z z i n i , S . C a r r a ,
E . Ai t i n i
1.Medical Oncology and
Hematology Department
2.Prevention Center of Female
Tu m o r s
Carlo Poma Hospital-Mantova-Italy
Special thanks for the support to I.O.M. – ISTITUTO ONCOLOGICO MANTOVANO