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Detection of LOH and mitochondrial DNA alterations in ductal lavage and nipple aspirate fluids from hngh-risk patients.

Abstract：

:We describe a method for the isolation of free DNA from ductal lavage (DL) and nipple aspirate fluid (NAF), and its evaluation for the presence of LOH at the BRCA1 and FHIT genes and for mitochondrial DNA (mtDNA) mutations at the D310 marker, to improve early detection of breast cancer. We evaluated 26 DL and six NAF samples from 14 women of known BRCA1 status, who have no clinical evidence of breast tumors: nine mutation carriers and five non-carriers. LOH studies at the BRCA1 locus were possible in 19/26 DL samples, and at the FHIT locus in 16/26 samples. In 4/9 mutation carriers we found LOH at the BRCA1 allele, and in two of these we also found LOH at the FHIT allele. In one of the mutation carriers with BRCA1 LOH, invasive breast cancer was subsequently detected, and the tumor showed the same LOH as the DL. In one of the true negatives, BRCA1 and FHIT LOH were detected. The mitochondrial studies were possible in all 26 DL samples and a somatic mutation was found in 3/9 carriers, two of whom also had LOH at the BRCA1 locus, and in none of the non-carriers. mtDNA mutation evaluation was possible in 4/6 NAF samples. The NAF and DL results were concordant. One NAF sample from a BRCA1 patient showed a mtDNA mutation. Our data demonstrates the feasibility of performing molecular studies using the free DNA present in the ductal fluid, while the intact cells can be used for cytologic studies.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Isaacs C,Cavalli LR,Cohen Y,Pennanen M,Shankar LK,Freedman M,Singh B,Liu M,Gallagher A,Rone JD,Dickson RB,Sidransky D,Haddad BR

doi

10.1023/B:BREA.0000018406.03679.2e

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

99-105

issue

2

eissn

0167-6806

issn

1573-7217

pii

5255062

journal_volume

84

pub_type

杂志文章

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