nach oben

01.09.2009 | Preclinical study

Genomic instability demonstrates similarity between DCIS and invasive carcinomas

verfasst von: Christopher M. Heaphy, Marco Bisoffi, Nancy E. Joste, Kathy B. Baumgartner, Richard N. Baumgartner, Jeffrey K. Griffith

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2009

Einloggen, um Zugang zu erhalten

Abstract

Purpose To assess telomere DNA content (TC) and the number of sites of allelic imbalance (AI) as a function of breast cancer progression. Experimental design TC and AI were determined in 54 histologically normal tissues, 10 atypical ductal hyperplasias (ADH), 122 in situ ductal carcinomas (DCIS) and 535 invasive carcinomas (Stage I–IIIA). Results TC was altered in ADH lesions (20%), DCIS specimens (53%) and invasive carcinomas (51%). The mean number of sites of AI was 0.26 in histologically normal group tissue, increased to 1.00 in ADH, 2.94 in DCIS, and 3.07 in invasive carcinomas. All groups were statistically different from the histologically normal group (P < 0.001 for each); however, there was no difference between DCIS and the invasive groups. Conclusions Genomic instability increases in ADH and plateaus in DCIS without further increase in the invasive carcinomas, supporting the notion that invasive carcinomas evolve from or in parallel with DCIS.

Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396:643–649. doi:10.1038/25292 PubMedCrossRef

Simpson PT, Reis-Filho JS, Gale T, Lakhani SR (2005) Molecular evolution of breast cancer. J Pathol 205:248–254. doi:10.1002/path.1691 PubMedCrossRef

Allred DC, Mohsin SK, Fuqua SA (2001) Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer 8:47–61. doi:10.1677/erc.0.0080047 PubMedCrossRef

Lo AW, Sabatier L, Fouladi B, Pottier G, Ricoul M, Murnane JP (2002) DNA amplification by breakage/fusion/bridge cycles initiated by spontaneous telomere loss in a human cancer cell line. Neoplasia 4:531–538. doi:10.1038/sj.neo.7900267 PubMedCrossRef

O’Hagan RC, Chang S, Maser RS, Mohan R, Artandi SE, Chin L et al (2002) Telomere dysfunction provokes regional amplification and deletion in cancer genomes. Cancer Cell 2:149–155. doi:10.1016/S1535-6108(02)00094-6 PubMedCrossRef

Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB et al (1992) Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 11:1921–1929PubMed

Chin K, de Solorzano CO, Knowles D, Jones A, Chou W, Rodriguez EG et al (2004) In situ analyses of genome instability in breast cancer. Nat Genet 36:984–988. doi:10.1038/ng1409 PubMedCrossRef

Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD et al (1988) A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA 85:6622–6626. doi:10.1073/pnas.85.18.6622 PubMedCrossRef

de Lange T (2002) Protection of mammalian telomeres. Oncogene 21:532–540. doi:10.1038/sj.onc.1205080 PubMedCrossRef

10.

Smogorzewska A, de Lange T (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73:177–208. doi:10.1146/annurev.biochem.73.071403.160049 PubMedCrossRef

11.

de Lange T, Shiue L, Myers RM, Cox DR, Naylor SL, Killery AM et al (1990) Structure and variability of human chromosome ends. Mol Cell Biol 10:518–527PubMed

12.

Saltman D, Morgan R, Cleary ML, de Lange T (1993) Telomeric structure in cells with chromosome end associations. Chromosoma 102:121–128. doi:10.1007/BF00356029 PubMedCrossRef

13.

Hande MP, Samper E, Lansdorp P, Blasco MA (1999) Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. J Cell Biol 144:589–601. doi:10.1083/jcb.144.4.589 PubMedCrossRef

14.

Olovnikov AM (1973) A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 41:181–190. doi:10.1016/0022-5193(73)90198-7 PubMedCrossRef

15.

Smogorzewska A, van Steensel B, Bianchi A, Oelmann S, Schaefer MR, Schnapp G et al (2000) Control of human telomere length by TRF1 and TRF2. Mol Cell Biol 20:1659–1668. doi:10.1128/MCB.20.5.1659-1668.2000 PubMedCrossRef

16.

Bohr VA, Anson RM (1995) DNA damage, mutation and fine structure DNA repair in aging. Mutat Res 338:25–34PubMed

17.

Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL et al (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015. doi:10.1126/science.7605428 PubMedCrossRef

18.

Meeker AK, Argani P (2004) Telomere shortening occurs early during breast tumorigenesis: a cause of chromosome destabilization underlying malignant transformation? J Mammary Gland Biol Neoplasia 9:285–296. doi:10.1023/B:JOMG.0000048775.04140.92 PubMedCrossRef

19.

Meeker AK, Hicks JL, Iacobuzio-Donahue CA, Montgomery EA, Westra WH, Chan TY et al (2004) Telomere length abnormalities occur early in the initiation of epithelial carcinogenesis. Clin Cancer Res 10:3317–3326. doi:10.1158/1078-0432.CCR-0984-03 PubMedCrossRef

20.

Meeker AK, Hicks JL, Gabrielson E, Strauss WM, De Marzo AM, Argani P (2004) Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma. Am J Pathol 164:925–935PubMed

21.

Heaphy CM, Bisoffi M, Fordyce CA, Haaland CM, Hines WC, Joste NE et al (2006) Telomere DNA content and allelic imbalance demonstrate field cancerization in histologically normal tissue adjacent to breast tumors. Int J Cancer 119:108–116. doi:10.1002/ijc.21815 PubMedCrossRef

22.

Fordyce CA, Heaphy CM, Bisoffi M, Wyaco JL, Joste NE, Mangalik A et al (2006) Telomere content correlates with stage and prognosis in breast cancer. Breast Cancer Res Treat 99:193–202. doi:10.1007/s10549-006-9204-1 PubMedCrossRef

23.

Heaphy CM, Baumgartner KB, Bisoffi M, Baumgartner RN, Griffith JK (2007) Telomere DNA content predicts breast cancer free survival interval. Clin Cancer Res 13:7037–7043. doi:10.1158/1078-0432.CCR-07-0432 PubMedCrossRef

24.

Balmain A, Gray J, Ponder B (2003) The genetics and genomics of cancer. Nat Genet 33(Suppl):238–244. doi:10.1038/ng1107 PubMedCrossRef

25.

Miyakis S, Spandidos DA (2002) Allelic loss in breast cancer. Cancer Detect Prev 26:426–434. doi:10.1016/S0361-090X(02)00128-9 PubMedCrossRef

26.

Farabegoli F, Champeme MH, Bieche I, Santini D, Ceccarelli C, Derenzini M et al (2002) Genetic pathways in the evolution of breast ductal carcinoma in situ. J Pathol 196:280–286. doi:10.1002/path.1048 PubMedCrossRef

27.

Ellsworth RE, Ellsworth DL, Love B, Patney HL, Hoffman LR, Kane J et al (2007) Correlation of levels and patterns of genomic instability with histological grading of DCIS. Ann Surg Oncol 14:3070–3077. doi:10.1245/s10434-007-9459-8 PubMedCrossRef

28.

O’Connell P, Pekkel V, Fuqua SA, Osborne CK, Clark GM, Allred DC (1998) Analysis of loss of heterozygosity in 399 premalignant breast lesions at 15 genetic loci. J Natl Cancer Inst 90:697–703. doi:10.1093/jnci/90.9.697 PubMedCrossRef

29.

Aubele MM, Cummings MC, Mattis AE, Zitzelsberger HF, Walch AK, Kremer M et al (2000) Accumulation of chromosomal imbalances from intraductal proliferative lesions to adjacent in situ and invasive ductal breast cancer. Diagn Mol Pathol 9:14–19. doi:10.1097/00019606-200003000-00003 PubMedCrossRef

30.

Ellsworth DL, Ellsworth RE, Love B, Deyarmin B, Lubert SM, Mittal V et al (2004) Genomic patterns of allelic imbalance in disease free tissue adjacent to primary breast carcinomas. Breast Cancer Res Treat 88:131–139. doi:10.1007/s10549-004-1424-7 PubMedCrossRef

31.

Deng G, Lu Y, Zlotnikov G, Thor AD, Smith HS (1996) Loss of heterozygosity in normal tissue adjacent to breast carcinomas. Science 274:2057–2059. doi:10.1126/science.274.5295.2057 PubMedCrossRef

32.

Forsti A, Louhelainen J, Soderberg M, Wijkstrom H, Hemminki K (2001) Loss of heterozygosity in tumour-adjacent normal tissue of breast and bladder cancer. Eur J Cancer 37:1372–1380. doi:10.1016/S0959-8049(01)00118-6 PubMedCrossRef

33.

Euhus DM, Cler L, Shivapurkar N, Milchgrub S, Peters GN, Leitch AM et al (2002) Loss of heterozygosity in benign breast epithelium in relation to breast cancer risk. J Natl Cancer Inst 94:858–860PubMed

34.

Moinfar F, Man YG, Arnould L, Bratthauer GL, Ratschek M, Tavassoli FA (2000) Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis. Cancer Res 60:2562–2566PubMed

35.

Ellsworth RE, Ellsworth DL, Lubert SM, Hooke J, Somiari RI, Shriver CD (2003) High-throughput loss of heterozygosity mapping in 26 commonly deleted regions in breast cancer. Cancer Epidemiol Biomarkers Prev 12:915–919PubMed

36.

Ellsworth RE, Ellsworth DL, Deyarmin B, Hoffman LR, Love B, Hooke JA et al (2005) Timing of critical genetic changes in human breast disease. Ann Surg Oncol 12:1054–1060. doi:10.1245/ASO.2005.03.522 PubMedCrossRef

37.

Baumgartner KB, Hunt WC, Baumgartner RN, Crumley DD, Gilliland FD, McTiernan A et al (2004) Association of body composition and weight history with breast cancer prognostic markers: divergent pattern for Hispanic and non-Hispanic White women. Am J Epidemiol 160:1087–1097. doi:10.1093/aje/kwh313 PubMedCrossRef

38.

Bryant JE, Hutchings KG, Moyzis RK, Griffith JK (1997) Measurement of telomeric DNA content in human tissues. Biotechniques 23:476–478, 480, 482PubMed

39.

Heaphy CM, Hines WC, Butler KS, Haaland CM, Heywood G, Fischer EG et al (2007) Assessment of the frequency of allelic imbalance in human tissue using a multiplex polymerase chain reaction system. J Mol Diagn 9:266–271. doi:10.2353/jmoldx.2007.060115 PubMedCrossRef

40.

Hiyama E, Hiyama K (2002) Clinical utility of telomerase in cancer. Oncogene 21:643–649. doi:10.1038/sj.onc.1205070 PubMedCrossRef

41.

Hines WC, Fajardo AM, Joste NE, Bisoffi M, Griffith JK (2005) Quantitative and spatial measurements of telomerase reverse transcriptase expression within normal and malignant human breast tissues. Mol Cancer Res 3:503–509. doi:10.1158/1541-7786.MCR-05-0031 PubMedCrossRef

Titel: Genomic instability demonstrates similarity between DCIS and invasive carcinomas
verfasst von: Christopher M. Heaphy
Marco Bisoffi
Nancy E. Joste
Kathy B. Baumgartner
Richard N. Baumgartner
Jeffrey K. Griffith
Publikationsdatum: 01.09.2009
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2009
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0165-4

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Springer Medizin

Genomic instability demonstrates similarity between DCIS and invasive carcinomas

Abstract

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

Sind Frauen die fähigeren Ärzte?

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

Sind Frauen die fähigeren Ärzte?

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Onkologie