Four regions of allelic imbalance on 17q12‐qter associated with high‐grade breast tumors

Rearrangements or loss of chromosome 17 are frequent events in breast tumors. Chromosome 17 contains at least four genes implicated in breast cancer (TP53, ERBB2 (Her2/neu), BRCA1, and NM23), as well as other putative tumor suppressor genes and oncogenes implicated in loss of heterozygosity or allelic imbalance studies. Allelic imbalance represents the addition or loss of genetic material in tumor samples, providing circumstantial evidence for the location of cancer related genes. We have analyzed a panel of 85 breast tumor/normal tissue pairs with 21 PCR‐based short tandem repeat (STR) markers located at 17q12‐qter to more precisely define regions of allelic imbalance and to determine their relation to clinical parameters. Our analysis revealed at least four common regions of allelic imbalance: proximal to BRCA1, including D17S800 (17q12); distal to NM23 around D17S787 (17q22); near the growth hormone (GH) locus, at D17S948 (17q23‐24); and between markers D17S937 and D17S802 (17q25). These data also reveal that loss (or gain) of 17q genetic material correlates with poorly differentiated (grade III) tumors (P = <0.001), high S phase fraction (P = 0.034), and positive TP53 immunohistochemical staining (P = 0.011). However, steroid receptor status, ERBB2 (Her2/neu) staining, and aneuploidy do not correlate with allelic imbalance at 17q. Genes Chromosomes Cancer 20:354–362, 1997. © 1997 Wiley‐Liss, Inc.

[1]  L. Adams,et al.  Mapping of 228 ESTs and 26 genes into an integrated physical and genetic map of human chromosome 17. , 1997, Genomics.

[2]  L. Adams,et al.  Localization of a growth suppressor activity in MCF7 breast cancer cells to chromosome 17q24-q25 , 1997, Oncogene.

[3]  K. Cooney,et al.  A region of interstitial 17q25 allelic loss in ovarian tumors coincides with a defined region of loss in breast tumors , 1997, Oncogene.

[4]  D. Niederacher,et al.  Patterns of allelic loss on chromosome 17 in sporadic breast carcinomas detected by fluorescent‐labeled microsatellite analysis , 1997, Genes, chromosomes & cancer.

[5]  Å. Borg,et al.  Loss of heterozygosity at 7q31 in breast cancer: results from an International Collaborative Study Group. The Breast Cancer Somatic Genetics Consortium. , 1997, Genes, chromosomes & cancer.

[6]  B. Karlan,et al.  DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies. , 1996, Oncogene.

[7]  E. Petty,et al.  Detailed deletion analysis of sporadic breast tumors defines an interstitial region of allelic loss on l7q25 , 1996, Genes, chromosomes & cancer.

[8]  Cécile Fizames,et al.  A comprehensive genetic map of the human genome based on 5,264 microsatellites , 1996, Nature.

[9]  J. Varley,et al.  Allelic imbalance in the region of the BRCA1 gene in ductal carcinoma in situ of the breast. , 1996, British Journal of Cancer.

[10]  L Kruglyak,et al.  An STS-Based Map of the Human Genome , 1995, Science.

[11]  R. Brown,et al.  Characterization of extensive genetic alterations in ductal carcinoma in situ by fluorescence in situ hybridization and molecular analysis. , 1995, Journal of the National Cancer Institute.

[12]  J. Varley,et al.  Detailed mapping and loss of heterozygosity analysis suggests a suppressor locus involved in sporadic breast cancer within a distal region of chromosome band 17p13.3. , 1995, Human molecular genetics.

[13]  N. Phillips,et al.  Allelotyping of ductal carcinoma in situ of the breast: deletion of loci on 8p, 13q, 16q, 17p and 17q. , 1995, Cancer research.

[14]  R. White,et al.  Suppression of malignant phenotype in a human prostate cancer cell line by fragments of normal chromosomal region 17q. , 1995, Cancer research.

[15]  S. Baylin,et al.  p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3 , 1995, Nature Genetics.

[16]  B. Johansson,et al.  Chromosome analysis of 97 primary breast carcinomas: Identification of eight karyotypic subgroups , 1995, Genes, chromosomes & cancer.

[17]  T. Katagiri,et al.  Association of genetic alterations on chromosome 17 and loss of hormone receptors in breast cancer. , 1995, British Journal of Cancer.

[18]  H. Scherthan,et al.  Suppression of tumorigenicity of breast cancer cells by transfer of human chromosome 17 does not require transferred BRCA1 and p53 genes. , 1995, Oncogene.

[19]  S. Mazoyer,et al.  Five distinct deleted regions on chromosome 17 defining different subsets of human primary breast tumors. , 1995, Oncology.

[20]  P. Devilee,et al.  Somatic genetic changes in human breast cancer. , 1994, Biochimica et biophysica acta.

[21]  J. Barrett,et al.  Differential suppression of mammary and prostate cancer metastasis by human chromosomes 17 and 11. , 1994, Cancer research.

[22]  M. Skolnick,et al.  BRCA1 mutations in primary breast and ovarian carcinomas. , 1994, Science.

[23]  C. Harris,et al.  Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. , 1994, Cancer research.

[24]  B. Ponder,et al.  Detailed deletion mapping of chromosome segment 17q12-21 in sporadic breast tumours. , 1994, Genes, chromosomes & cancer.

[25]  P. Steeg,et al.  NME1 protein expression and loss of heterozygosity mutations in primary human breast tumors. , 1994, Journal of the National Cancer Institute.

[26]  B. Dutrillaux,et al.  Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique , 1994, Genes, chromosomes & cancer.

[27]  Cécile Fizames,et al.  The 1993–94 Généthon human genetic linkage map , 1994, Nature Genetics.

[28]  C. Croce,et al.  Tumor and growth suppression of breast cancer cells by chromosome 17-associated functions. , 1994, Cancer research.

[29]  J Piper,et al.  Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[30]  R. Zeillinger,et al.  Patterns of allele losses suggest the existence of five distinct regions of loh on chromosome 17 in breast cancer , 1994, International journal of cancer.

[31]  P. Meltzer,et al.  Identification of cryptic sites of DNA sequence amplification in human breast cancer by chromosome microdissection , 1994, Nature Genetics.

[32]  R. Lidereau,et al.  Identification of three regions on chromosome 17q in primary human breast carcinomas which are frequently deleted. , 1993, Cancer research.

[33]  G. Casey,et al.  Functional evidence for a breast cancer growth suppressor gene on chromosome 17. , 1993, Human molecular genetics.

[34]  K. Heimdal,et al.  Prognostic significance of TP53 alterations in breast carcinoma. , 1993, British Journal of Cancer.

[35]  Hisayoshi Kondo,et al.  Reduced expression of nm23‐H1, but not of nm23‐H2, is concordant with the frequency of lymph‐node metastasis of human breast cancer , 1993, International journal of cancer.

[36]  J. Trent,et al.  Clonal chromosome abnormalities in human breast carcinomas I. Twenty‐eight cases with primary disease , 1993, Genes, chromosomes & cancer.

[37]  P. Devilee,et al.  PCR-based microsatellite polymorphisms in the detection of loss of heterozygosity in fresh and archival tumour tissue. , 1993, British Journal of Cancer.

[38]  U. Veronesi,et al.  p53 as an independent prognostic marker in lymph node-negative breast cancer patients. , 1993, Journal of the National Cancer Institute.

[39]  P. Devilee,et al.  Allele loss patterns on chromosome 17q in 109 breast carcinomas indicate at least two distinct target regions. , 1993, Oncogene.

[40]  W. McGuire,et al.  Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. , 1993, Journal of the National Cancer Institute.

[41]  E. Kawasaki,et al.  Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. , 1992, Journal of the National Cancer Institute.

[42]  J. Barrett,et al.  Detection of frequent allelic loss on proximal chromosome 17q in sporadic breast carcinoma using microsatellite length polymorphisms. , 1992, Cancer research.

[43]  J. Nesland,et al.  Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas , 1992, Genes, chromosomes & cancer.

[44]  Y. Nakamura,et al.  Accumulation of genetic alterations and progression of primary breast cancer. , 1991, Cancer research.

[45]  R. Tubbs,et al.  Improved sensitivity and resolution in the flow cytometric DNA analysis of human solid tumor specimens. Use of in vitro fine-needle aspiration and uniform staining reagents. , 1991, American journal of clinical pathology.

[46]  B. Vogelstein,et al.  p53 mutations in human cancers. , 1991, Science.

[47]  P. Devilee,et al.  Frequent somatic imbalance of marker alleles for chromosome 1 in human primary breast carcinoma. , 1991, Cancer research.

[48]  W. Bodmer,et al.  p53 mutations in colorectal cancer. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[49]  M. Lagios Duct carcinoma in situ. Pathology and treatment. , 1990, The Surgical clinics of North America.

[50]  L. Holmberg,et al.  Chapter I. Biology and natural history of breast cancer , 1990, International journal of cancer. Supplement = Journal international du cancer. Supplement.

[51]  S Friedman,et al.  Prognostic value of histologic grade nuclear components of Scarff‐Bloom‐Richardson (SBR). An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas , 1989, Cancer.

[52]  L. Liotta,et al.  Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. , 1989, Cancer research.

[53]  W Godolphin,et al.  Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. , 1989, Science.

[54]  H. W. Simpson,et al.  GENESIS OF BREAST CANCER IS IN THE PREMENOPAUSE , 1988, The Lancet.

[55]  B. Vogelstein,et al.  Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. , 1985, Biochemical and biophysical research communications.