Melanie Barbara Boettger1, Consolato Sergi2, Peter Meyer3
1Institute of Human Genetics, University of Heidelberg, 69120 Heidelberg, Germany
2Institute of Pathology, University of Heidelberg, 69120 Heidelberg, Germany
3Institute of Human Genetics, University of Heidelberg, 69120 Heidelberg; Genefinder Technologies Ltd., Sperberstr. 2, D-81827 Munich, Germany
DOI: 10.1186/1477-3163-2-5
ABSTRACT
Background: Germline mutations in BRCA1/2 greatly elevate risks of breast and ovarian cancers, but the role of these genes in tumourigenesis of other cancer types is still being investigated.
Objective: We report on an investigation of BRCA1/2 mutations and their loss of heterozygosity (LOH) in a patient with a strong family history of breast cancer who was diagnosed with consecutive primary cervical, ovarian and lung carcinomas.
Methods and Results: BRCA1/2 mutation screening of the proband revealed a common familial breast- and ovarian cancer-associated germline BRCA2 mutation (3034del4bp). We then performed LOH analysis for BRCA2 in lung adenocarcinoma tissue of the patient. Using the laser-capture microdissection (LCM) technique, we obtained pure populations of neoplastic cells from which DNA could be extracted. Mutation analysis by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing revealed loss of the mutant allele in the adenocarcinoma tumour tissue.
Conclusion: To our knowledge, this is the first report of investigation for LOH for BRCA2 in primary lung adenocarcinoma tissue of a patient with multiple primary tumours related to a familial germline BRCA2 mutation. Interestingly, it was the mutant, not the wild-type, allele which was lost in the lung adenocarcinoma tissue.
Keywords: loss of heterozygosity (LOH), BRCA2 germline mutation, lung adenocarcinoma, cancer genetics, familial breast cancer.