TY - JOUR
T1 - Genetic divergence in the clonal evolution of breast cancer
AU - Fujii, Hiroaki
AU - Marsh, Carla
AU - Cairns, Paul
AU - Sidransky, David
AU - Gabrielson, Edward
PY - 1996/4/1
Y1 - 1996/4/1
N2 - The progression of ductal carcinoma in situ (DCIS) to infiltrating and metastatic cancer of the breast is thought to be a consequence of clonal expansions of neoplastic cells with progressively more genetic alterations. To study this progression, we first dissected multiple foci from each of 23 breast tumors with DCIS only and 20 cases with synchronous DCIS and infiltrating cancer. We then tested microsatellite markers by PCR for allelic losses in the individual loci for loci on chromosomes 6q, 9p, 11q, 13q, 16q, 17q, and 17p. The patterns of allelic losses identified in the in situ cancers were generally conserved in the synchronous infiltrating tumors, supporting the paradigm that the infiltrating tumors are clonally derived from the in situ lesions. However, in 8 (40%) of the 20 cases with synchronous in situ and invasive cancer, heterogeneous patterns of allelic loss at one or more chromosomal loci were observed in adjacent DCIS foci. Moreover, some of the allelic losses recognized in in situ portions of the tumors were not conserved in the clonal progression to the synchronous invasive tumor. Such allelic loss heterogeneity was noted in only I of the 20 infiltrating tumors and only 3 of the 23 cases of DCIS without invasion that were studied in a similar manner. This heterogeneity indicates genetic divergence during the clonal evolution of breast cancer, particularly at the time when in situ cancers progress to invasive cancers.
AB - The progression of ductal carcinoma in situ (DCIS) to infiltrating and metastatic cancer of the breast is thought to be a consequence of clonal expansions of neoplastic cells with progressively more genetic alterations. To study this progression, we first dissected multiple foci from each of 23 breast tumors with DCIS only and 20 cases with synchronous DCIS and infiltrating cancer. We then tested microsatellite markers by PCR for allelic losses in the individual loci for loci on chromosomes 6q, 9p, 11q, 13q, 16q, 17q, and 17p. The patterns of allelic losses identified in the in situ cancers were generally conserved in the synchronous infiltrating tumors, supporting the paradigm that the infiltrating tumors are clonally derived from the in situ lesions. However, in 8 (40%) of the 20 cases with synchronous in situ and invasive cancer, heterogeneous patterns of allelic loss at one or more chromosomal loci were observed in adjacent DCIS foci. Moreover, some of the allelic losses recognized in in situ portions of the tumors were not conserved in the clonal progression to the synchronous invasive tumor. Such allelic loss heterogeneity was noted in only I of the 20 infiltrating tumors and only 3 of the 23 cases of DCIS without invasion that were studied in a similar manner. This heterogeneity indicates genetic divergence during the clonal evolution of breast cancer, particularly at the time when in situ cancers progress to invasive cancers.
UR - http://www.scopus.com/inward/record.url?scp=0029914919&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029914919&partnerID=8YFLogxK
M3 - Article
C2 - 8603391
AN - SCOPUS:0029914919
SN - 0008-5472
VL - 56
SP - 1493
EP - 1497
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -