Accession Number:

ADA434094

Title:

Detection of Mitochondrial DNA Mutations in Mammary Epithelial Cells in Nipple Aspirate Fluid

Descriptive Note:

Final rept. 1 Sep 2001-31 Aug 2004

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

2004-09-01

Pagination or Media Count:

24.0

Abstract:

We have successfully developed a method to isolate free DNA from ductal lavage DL and nipple aspirate fluid NAF, and to use the isolated DNA for mitochondrial DNA mtDNA mutation analysis and LOH studies in order to improve early detection of breast cancer. We evaluated 26 DL and six NAF samples from 14 women of known BRAC1 status 9 carriers and 5 non-carriers, with no clinical evidence of breast tumors. LOH studies at the BRAC1 locus were possible in 1926 DL samples, and at the FHIT locus in 1626 samples. In 49 mutation carriers we found LOH at the BRAC1 allele, and in 2 of these we also found LOH at the FHIT allele. In one of the mutation carriers with BRAC1 LOH, invasive breast cancer was subsequently detected, and the tumor showed the same LOH as the DL. In one of the true negatives, BRAC1 and FHIT LOH were detected. The mitochondrial studies were possible in all 26 DL samples and a somatic mutation at the D310 marker was found in 39 carriers, 2 of whom also had LOH were detected. The mitochondrial studies were possible in all 26 DL samples and a somatic mutation at the D310 marker was found in 39 carriers, 2 of whom also has LOH at the BRAC1 locus, and in none of the non-carriers, mtDNA mutation evaluation was possible in 46 NAF samples. The NAF and DL results were concordant. One NAF sample from a BRCA1 patient showed a mtDNA mutation. Our data demonstrated the feasibility of molecular studies using the free DNA present in the ductal fluid, while the intact cells can be used for cytologic studies.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE