nach oben

Breast Cancer Research and Treatment

Erschienen in:

01.11.2008 | Epidemiology

Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations

verfasst von: Zdenek Kleibl, Ondrej Havranek, Jan Novotny, Petra Kleiblova, Pavel Soucek, Petr Pohlreich

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2008

Einloggen, um Zugang zu erhalten

Abstract

The CHEK2 gene mutations I157T (c.470T > C) and IVS2 + 1G > A affecting the forkhead-associated domain (FHA) have been shown to increase the risk of breast cancer development in several populations. We analyzed the CHEK2 gene segment coding for FHA domain in 673 unselected breast cancer patients and 683 controls from the Czech Republic using the denaturant high-performance liquid chromatography. The found frequency of predominant FHA alteration I157T did not differ between breast cancer patients (19/673; 2.82%) and controls (17/683; 2.49%; P = 0.71). Besides this mutation we characterized another nine alterations—six located within FHA coding sequence and three occurring in introns 1 or 2). Eight variants occurred once each in patients with breast cancer and two were present in controls. Three alterations found in breast cancer patients were novel missense variants (Y159H, T172A, and L174F) affecting highly conservative residues in FHA domain. Despite the lack of association of I157T mutation with breast cancer development in our population we deduced that the FHA domain is the subject of rare population-specific alterations that might modify risk of various cancers.

Nevanlinna H, Bartek J (2006) The CHEK2 gene and inherited breast cancer susceptibility. Oncogene 25:5912–5919PubMedCrossRef

Cybulski C, Gorski B, Huzarski T, Masojc B, Mierzejewski M, Debniak T et al (2004) CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet 75:1131–1135PubMedCrossRef

Prokopcova J, Kleibl Z, Banwell CM, Pohlreich P (2007) The role of ATM in breast cancer development. Breast Cancer Res Treat 104:121–128PubMedCrossRef

Matsuoka S, Huang M, Elledge SJ (1998) Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282:1893–1897PubMedCrossRef

Falck J, Lukas C, Protopopova M, Lukas J, Selivanova G, Bartek J (2001) Functional impact of concomitant versus alternative defects in the Chk2-p53 tumour suppressor pathway. Oncogene 20:5503–5510PubMedCrossRef

Bartek J, Lukas J (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3:421–429PubMedCrossRef

Traven A, Heierhorst J (2005) SQ/TQ cluster domains: concentrated ATM/ATR kinase phosphorylation site regions in DNA-damage-response proteins. Bioessays 27:397–407PubMedCrossRef

Yoda A, Xu XZ, Onishi N, Toyoshima K, Fujimoto H, Kato N et al (2006) Intrinsic kinase activity and SQ/TQ domain of Chk2 kinase as well as N-terminal domain of Wip1 phosphatase are required for regulation of Chk2 by Wip1. J Biol Chem 281:24847–24862PubMedCrossRef

Durocher D, Jackson SP (2002) The FHA domain. FEBS Lett 513:58–66PubMedCrossRef

10.

Oliver AW, Paul A, Boxall KJ, Barrie SE, Aherne GW, Garrett MD et al (2006) Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange. EMBO J 25:3179–3190PubMedCrossRef

11.

Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE et al (1999) Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286:2528–2531PubMedCrossRef

12.

Sodha N, Houlston RS, Bullock S, Yuille MA, Chu C, Turner G et al (2002) Increasing evidence that germline mutations in CHEK2 do not cause Li-Fraumeni syndrome. Hum Mutat 20:460–462PubMedCrossRef

13.

The CHEK2 Breast Cancer Case-Control Consortium (2004) CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 74:1175–1182 CrossRef

14.

Chekmariova EV, Sokolenko AP, Buslov KG, Iyevleva AG, Ulibina YM, Rozanov ME et al (2007) CHEK2 1100delC mutation is frequent among Russian breast cancer patients. Breast Cancer Res Treat 100:281–286

15.

Osorio A, Rodriguez-Lopez R, Diez O, de la Hoya M, Ignacio MJ, Vega A et al (2004) The breast cancer low-penetrance allele 1100delC in the CHEK2 gene is not present in Spanish familial breast cancer population. Int J Cancer 108:54–56PubMedCrossRef

16.

Falchetti M, Lupi R, Rizzolo P, Ceccarelli K, Zanna I, Calo V et al. (2007) BRCA1/BRCA2 rearrangements and CHEK2 common mutations are infrequent in Italian male breast cancer cases. Breast Cancer Res Treat: DOI 10.1007/s10549-007-9689-2

17.

Gonzalez-Hormazabal P, Castro VG, Blanco R, Gomez F, Peralta O, Waugh E et al. (2007) Absence of CHEK2 1100delC mutation in familial breast cancer cases from a South American population. Breast Cancer Res Treat: DOI 10.1007/s10549-007-9743-0

18.

Song CG, Hu Z, Yuan WT, Di GH, Shen ZZ, Huang W et al (2006) CHEK2 c.1100delC may not contribute to genetic background of hereditary breast cancer from Shanghai of China. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 23:443–445PubMed

19.

Walsh T, Casadei S, Coats KH, Swisher E, Stray SM, Higgins J et al (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295:1379–1388PubMedCrossRef

20.

Wu X, Webster SR, Chen J (2001) Characterization of tumor-associated Chk2 mutations. J Biol Chem 276:2971–2974PubMedCrossRef

21.

Dufault MR, Betz B, Wappenschmidt B, Hofmann W, Bandick K, Golla A et al (2004) Limited relevance of the CHEK2 gene in hereditary breast cancer. Int J Cancer 110:320–325PubMedCrossRef

22.

Kleibl Z, Novotny J, Bezdickova D, Malik R, Kleiblova P, Foretova L et al (2005) The CHEK2 c.1100delC germline mutation rarely contributes to breast cancer development in the Czech Republic. Breast Cancer Res Treat 90:165–167PubMedCrossRef

23.

Schutte M, Seal S, Barfoot R, Meijers-Heijboer H, Wasielewski M, Evans DG et al (2003) Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. Am J Hum Genet 72:1023–1028PubMedCrossRef

24.

Sodha N, Bullock S, Taylor R, Mitchell G, Guertl-Lackner B, Williams RD et al (2002) CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours. Br J Cancer 87:1445–1448PubMedCrossRef

25.

Dong X, Wang L, Taniguchi K, Wang X, Cunningham JM, McDonnell SK et al (2003) Mutations in CHEK2 associated with prostate cancer risk. Am J Hum Genet 72:270–280PubMedCrossRef

26.

Vahteristo P, Bartkova J, Eerola H, Syrjakoski K, Ojala S, Kilpivaara O et al (2002) A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet 71:432–438PubMedCrossRef

27.

Bogdanova N, Enssen-Dubrowinskaja N, Feshchenko S, Lazjuk GI, Rogov YI, Dammann O et al (2005) Association of two mutations in the CHEK2 gene with breast cancer. Int J Cancer 116:263–266PubMedCrossRef

28.

Kilpivaara O, Vahteristo P, Falck J, Syrjakoski K, Eerola H, Easton D et al (2004) CHEK2 variant I157T may be associated with increased breast cancer risk. Int J Cancer 111:543–547PubMedCrossRef

29.

Cybulski C, Gorski B, Huzarski T, Byrski T, Gronwald J, Debniak T et al (2006) CHEK2-positive breast cancers in young Polish women. Clin Cancer Res 12:4832–4835PubMedCrossRef

30.

Bell DW, Kim SH, Godwin AK, Schiripo TA, Harris PL, Haserlat SM et al (2007) Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts. Int J Cancer 121:2661–2667PubMedCrossRef

31.

Brennan P, McKay J, Moore L, Zaridze D, Mukeria A, Szeszenia-Dabrowska N et al (2007) Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case control study. Hum Mol Genet 16:1794–1801PubMedCrossRef

32.

Sullivan A, Yuille M, Repellin C, Reddy A, Reelfs O, Bell A et al (2002) Concomitant inactivation of p53 and Chk2 in breast cancer. Oncogene 21:1316–1324PubMedCrossRef

33.

Miller CW, Ikezoe T, Krug U, Hofmann WK, Tavor S, Vegesna V et al (2002) Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. Genes Chromosomes Cancer 33:17–21PubMedCrossRef

34.

Smith PJ, Zhang C, Wang J, Chew SL, Zhang MQ, Krainer AR (2006) An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers. Hum Mol Genet 15:2490–2508PubMedCrossRef

35.

Huzarski T, Cybulski C, Domagala W, Gronwald J, Byrski T, Szwiec M et al (2005) Pathology of breast cancer in women with constitutional CHEK2 mutations. Breast Cancer Res Treat 90:187–189PubMedCrossRef

Titel: Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations
verfasst von: Zdenek Kleibl
Ondrej Havranek
Jan Novotny
Petra Kleiblova
Pavel Soucek
Petr Pohlreich
Publikationsdatum: 01.11.2008
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2008
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-007-9838-7

Neu im Fachgebiet Onkologie

NSCLC: Progressionsfreies Überleben unter Osimertinib fast versiebenfacht

06.06.2024 ASCO 2024 Kongressbericht

Erste Ergebnisse der Phase-III-Studie LAURA etablieren Osimertinib als neuen Therapiestandard für Menschen mit nicht-resezierbarem, EGFR-mutiertem, nicht-kleinzelligem Lungenkarzinom im Stadium III, die nach definitiver Radiochemotherapie progressionsfrei sind. Auf der ASCO-Tagung wurden diese beeindruckenden Ergebnisse besprochen.

Hodgkin Lymphom: BrECADD-Regime übertrifft die Erwartungen

05.06.2024 ASCO 2024 Kongressbericht

Das Kombinationsregime BrECADD mit Brentuximab vedotin ermöglichte in der Studie HD21 beim fortgeschrittenen klassischen Hodgkin-Lymphom eine unerwartet hohe progressionsfreie Überlebensrate von 94,3% nach vier Jahren. Gleichzeitig war das Regime besser tolerabel als der bisherige Standard eBEACOPP.

Antikörper-Drug-Konjugat verdoppelt PFS bei Multiplem Myelom

05.06.2024 ASCO 2024 Nachrichten

Zwei Phase-3-Studien deuten auf erhebliche Vorteile des Antikörper-Wirkstoff-Konjugats Belantamab-Mafodotin bei vorbehandelten Personen mit Multiplem Myelom: Im Vergleich mit einer Standard-Tripeltherapie wurde das progressionsfreie Überleben teilweise mehr als verdoppelt.

Neuer TKI gegen CML: Höhere Wirksamkeit, seltener Nebenwirkungen

05.06.2024 Chronische myeloische Leukämie Nachrichten

Der Tyrosinkinasehemmer (TKI) Asciminib ist älteren Vertretern dieser Gruppe bei CML offenbar überlegen: Personen mit frisch diagnostizierter CML entwickelten damit in einer Phase-3-Studie häufiger eine gute molekulare Response, aber seltener ernste Nebenwirkungen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

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

Weitere Artikel der Ausgabe 1/2008

In situ levels of oestrogen producing enzymes and its prognostic significance in postmenopausal breast cancer patients

Nonsteroidal anti-inflammatory drugs (NSAIDs) and mammographic density

Single nucleotide polymorphisms of the aromatase gene (CYP19A1), HER2/neu status, and prognosis in breast cancer patients

Routine prophylactic granulocyte colony stimulating factor (GCSF) is not necessary with accelerated (dose dense) paclitaxel for early breast cancer