TY - JOUR
T1 - Genetic aberrations in hypodiploid breast cancer
T2 - Frequent loss of chromosome 4 and amplification of cyclin D1 oncogene
AU - Tanner, Minna M.
AU - Karhu, Ritva A.
AU - Nupponen, Nina N.
AU - Borg, Åke
AU - Baldetorp, Bo
AU - Pejovic, Tanja
AU - Fernö, Mårten
AU - Killander, Dick
AU - Isola, Jorma J.
N1 - Funding Information:
Supported by the Finnish Cancer Foundation, the Scientific Foundation of Tampere University Hospital, the Swedish Cancer Society, the Mrs. Berta Kamprads Foundation, the Gunnar, Arvid, and Elisabeth Nilsson Foundation, the John and Augusta Persson Foundation, the Inga-Britt and Arne Lundberg Foundation, the Franke and Margareta Bergquist Foundation, the Anna-Lisa and Sven-Erik Lundgren Foundation, and the Hospital of Lund Foundation.
PY - 1998/7
Y1 - 1998/7
N2 - The evolution of somatic genetic aberrations in breast cancer has remained poorly understood. The most common chromosomal abnormality is hyperdiploidy, which is thought to arise via a transient hypodiploid state. However, hypodiploidy persists in 1 to 2% of breast tumors, which are characterized by a poor prognosis. We studied the genetic aberrations in 15 flow cytometrically hypodiploid breast cancers by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). Surprisingly, numerous copy number gains were detected in addition to the copy number losses. The number of gains per tumor was 4.3 ± 3.2 and that of losses was 4.5 ± 3.3 (mean ± SD), which is similar to that previously observed in hyperdiploid breast cancers. Gains at chromosomes or chromosomal regions at 11q13, 1q, 19, and 16p and losses of 2q, 4, 6q, 9p, 13, and 18 were most commonly observed. Compared with unselected breast carcinomas, hypodiploid tumors showed certain differences. Loss of chromosome 4 (53%) and gain of 11q13 (60%) were significantly more common in hypodiploid tumors. The gain at 11q13 was found by FISH to harbor amplification of the Cyclin D1 oncogene, which is therefore three to four times more common in hypodiploid than in unselected breast cancers (15 to 20%). Structural chromosomal aberrations (such as Cyclin D1 amplification) were present both in diploid and hypodiploid tumor cell populations, as assessed by FISH and CGH after flow cytometric sorting. Together these results indicate that hypodiploid tumors form a distinct genetic entity of invasive breast cancer, although they probably share a common genetic evolution pathway where structural chromosomal aberrations precede gross DNA ploidy changes.
AB - The evolution of somatic genetic aberrations in breast cancer has remained poorly understood. The most common chromosomal abnormality is hyperdiploidy, which is thought to arise via a transient hypodiploid state. However, hypodiploidy persists in 1 to 2% of breast tumors, which are characterized by a poor prognosis. We studied the genetic aberrations in 15 flow cytometrically hypodiploid breast cancers by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). Surprisingly, numerous copy number gains were detected in addition to the copy number losses. The number of gains per tumor was 4.3 ± 3.2 and that of losses was 4.5 ± 3.3 (mean ± SD), which is similar to that previously observed in hyperdiploid breast cancers. Gains at chromosomes or chromosomal regions at 11q13, 1q, 19, and 16p and losses of 2q, 4, 6q, 9p, 13, and 18 were most commonly observed. Compared with unselected breast carcinomas, hypodiploid tumors showed certain differences. Loss of chromosome 4 (53%) and gain of 11q13 (60%) were significantly more common in hypodiploid tumors. The gain at 11q13 was found by FISH to harbor amplification of the Cyclin D1 oncogene, which is therefore three to four times more common in hypodiploid than in unselected breast cancers (15 to 20%). Structural chromosomal aberrations (such as Cyclin D1 amplification) were present both in diploid and hypodiploid tumor cell populations, as assessed by FISH and CGH after flow cytometric sorting. Together these results indicate that hypodiploid tumors form a distinct genetic entity of invasive breast cancer, although they probably share a common genetic evolution pathway where structural chromosomal aberrations precede gross DNA ploidy changes.
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U2 - 10.1016/S0002-9440(10)65560-5
DO - 10.1016/S0002-9440(10)65560-5
M3 - Article
C2 - 9665480
AN - SCOPUS:0031870654
SN - 0002-9440
VL - 153
SP - 191
EP - 199
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -