Genetic divergence in the clonal evolution of breast cancer

Hiroaki Fujii, Carla Marsh, Paul Cairns, David Sidransky, Edward Gabrielson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1493-1497
Number of pages5
JournalCancer Research
Volume56
Issue number7
StatePublished - Apr 1 1996

Fingerprint

Clonal Evolution
Breast Neoplasms
Carcinoma, Intraductal, Noninfiltrating
Loss of Heterozygosity
Neoplasms
Genetic Heterogeneity
Microsatellite Repeats
Chromosomes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Genetic divergence in the clonal evolution of breast cancer. / Fujii, Hiroaki; Marsh, Carla; Cairns, Paul; Sidransky, David; Gabrielson, Edward.

In: Cancer Research, Vol. 56, No. 7, 01.04.1996, p. 1493-1497.

Research output: Contribution to journalArticle

Fujii, H, Marsh, C, Cairns, P, Sidransky, D & Gabrielson, E 1996, 'Genetic divergence in the clonal evolution of breast cancer', Cancer Research, vol. 56, no. 7, pp. 1493-1497.
Fujii, Hiroaki ; Marsh, Carla ; Cairns, Paul ; Sidransky, David ; Gabrielson, Edward. / Genetic divergence in the clonal evolution of breast cancer. In: Cancer Research. 1996 ; Vol. 56, No. 7. pp. 1493-1497.
@article{bbcb302db18e4c389be9ae947a2a20e3,
title = "Genetic divergence in the clonal evolution of breast cancer",
abstract = "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.",
author = "Hiroaki Fujii and Carla Marsh and Paul Cairns and David Sidransky and Edward Gabrielson",
year = "1996",
month = "4",
day = "1",
language = "English (US)",
volume = "56",
pages = "1493--1497",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

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

VL - 56

SP - 1493

EP - 1497

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 7

ER -