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Genetic Predictors of Adverse Radiotherapy Effects: The Gene-PARE project

      Purpose: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal.
      Methods and Materials: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work.
      Results: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy.
      Conclusions: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.

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      References

        • Anscher M.S.
        • Vujaskovic Z.
        Mechanisms and potential targets for prevention and treatment of normal tissue injury after radiation therapy.
        Semin Oncol. 2005; 32: S86-S91
        • McBride W.H.
        • Chiang C.S.
        • Olson J.L.
        • et al.
        A sense of danger from radiation.
        Radiat Res. 2004; 162: 1-19
        • Stone H.B.
        • Coleman C.N.
        • Anscher M.S.
        • et al.
        Effects of radiation on normal tissue.
        Lancet Oncol. 2003; 4: 529-536
        • Denham J.W.
        • Hauer-Jensen M.
        The radiotherapeutic injury—a complex ‘wound.’.
        Radiother Oncol. 2002; 63: 129-145
        • Hall E.J.
        Do no harm—normal tissue effects.
        Acta Oncol. 2001; 40: 913-916
        • Bentzen S.M.
        • Overgaard J.
        Patient-to-patient variability in the expression of radiation-induced normal tissue injury.
        Semin Radiat Oncol. 1994; 4: 68-80
        • Jackson A.
        • Kutcher G.J.
        • Yorke E.D.
        Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation.
        Med Phys. 1993; 20: 613-625
        • Tucker S.L.
        • Turesson I.
        • Thames H.D.
        Evidence for individual differences in the radiosensitivity of human skin.
        Eur J Cancer. 1992; 28A: 1783-1791
        • Fernet M.
        • Hall J.
        Genetic biomarkers of therapeutic radiation sensitivity.
        DNA Repair (Amst). 2004; 3: 1237-1243
        • Baumann M.
        • Holscher T.
        • Begg A.C.
        Towards genetic prediction of radiation responses.
        Radiother Oncol. 2003; 69: 121-125
        • Andreassen C.N.
        • Alsner J.
        • Overgaard J.
        Does variability in normal tissue reactions after radiotherapy have a genetic basis—where and how to look for it?.
        Radiother Oncol. 2002; 64: 131-140
        • Andreassen C.N.
        Can risk of radiotherapy-induced normal tissue complications be predicted from genetic profiles?.
        Acta Oncol. 2005; 44: 801-815
        • Jones I.M.
        • Thomas C.B.
        • Xi T.
        • et al.
        The genetic basis for variation in radiation sensitivity in the general population.
        Radiat Res. 2005; 163: 700-701
        • Bourguignon M.H.
        • Gisone P.A.
        • Perez M.R.
        • et al.
        Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection.
        Eur J Nucl Med Mol Imaging. 2005; 32: 351-368
        • Safwat A.
        • Bentzen S.M.
        • Turesson I.
        • et al.
        Deterministic rather than stochastic factors explain most of the variation in the expression of skin telangiectasia after radiotherapy.
        Int J Radiat Oncol Biol Phys. 2002; 52: 198-204
        • Tucker S.L.
        • Geara F.B.
        • Peters L.J.
        • et al.
        How much could the radiotherapy dose be altered for individual patients based on a predictive assay of normal-tissue radiosensitivity?.
        Radiother Oncol. 1996; 38: 103-113
        • Turesson I.
        • Joiner M.C.
        Clinical evidence of hypersensitivity to low doses in radiotherapy.
        Radiother Oncol. 1996; 40: 1-3
        • Fletcher G.H.
        Regaud lecture perspectives on the history of radiotherapy.
        Radiother Oncol. 1988; (12:iii–v): 253-271
        • Mackay R.I.
        • Hendry J.H.
        The modelled benefits of individualizing radiotherapy patients’ dose using cellular radiosensitivity assays with inherent variability.
        Radiother Oncol. 1999; 50: 67-75
        • Evans W.E.
        • Relling M.V.
        Moving towards individualized medicine with pharmacogenomics.
        Nature. 2004; 429: 464-468
        • Fierz W.
        Challenge of personalized health care.
        Med Sci Monit. 2004; 10: RA111-RA123
        • Gurwitz D.
        • Livshits G.
        Personalized Medicine Europe: Health, Genes and Society: Tel-Aviv University, Tel-Aviv, Israel, June 19–21, 2005.
        Eur J Hum Genet. 2006; 14: 376-380
        • Agren A.
        • Brahme A.
        • Turesson I.
        Optimization of uncomplicated control for head and neck tumors.
        Int J Radiat Oncol Biol Phys. 1990; 19: 1077-1085
        • MacKay R.I.
        • Niemierko A.
        • Goitein M.
        • et al.
        Potential clinical impact of normal-tissue intrinsic radiosensitivity testing.
        Radiother Oncol. 1998; 46: 215-216
        • Dubray B.
        • Pavy J.J.
        • Giraud P.
        • et al.
        [Predictive tests of response to radiotherapy. Assessment and perspectives in 1997].
        Cancer Radiother. 1997; 1 (in French): 473-483
        • Loeffler J.S.
        • Harris J.R.
        • Dahlberg W.K.
        • et al.
        In vitro radiosensitivity of human diploid fibroblasts derived from women with unusually sensitive clinical responses to definitive radiation therapy for breast cancer.
        Radiat Res. 1990; 121: 227-231
        • Oppitz U.
        • Baier K.
        • Wulf J.
        • et al.
        The in vitro colony assay.
        Int J Radiat Biol. 2001; 77: 105-110
        • Akudugu J.M.
        • Bell R.S.
        • Catton C.
        • et al.
        Wound healing morbidity in STS patients treated with preoperative radiotherapy in relation to in vitro skin fibroblast radiosensitivity, proliferative capacity and TGF-beta activity.
        Radiother Oncol. 2006; 78: 17-26
        • Begg A.C.
        • Russell N.S.
        • Knaken H.
        • et al.
        Lack of correlation of human fibroblast radiosensitivity in vitro with early skin reactions in patients undergoing radiotherapy.
        Int J Radiat Biol. 1993; 64: 393-405
        • Stewart C.C.
        • Stevenson A.P.
        • Habbersett R.C.
        The effect of low-dose irradiation on unstimulated and PHA-stimulated human lymphocyte subsets.
        Int J Radiat Biol Relat Stud Phys Chem Med. 1988; 53: 77-87
        • Crompton N.E.
        • Ozsahin M.
        A versatile and rapid assay of radiosensitivity of peripheral blood leukocytes based on DNA and surface-marker assessment of cytotoxicity.
        Radiat Res. 1997; 147: 55-60
        • Crompton N.E.
        • Miralbell R.
        • Rutz H.P.
        • et al.
        Altered apoptotic profiles in irradiated patients with increased toxicity.
        Int J Radiat Oncol Biol Phys. 1999; 45: 707-714
        • Crompton N.E.
        • Shi Y.Q.
        • Emery G.C.
        • et al.
        Sources of variation in patient response to radiation treatment.
        Int J Radiat Oncol Biol Phys. 2001; 49: 547-554
        • Ozsahin M.
        • Ozsahin H.
        • Shi Y.
        • et al.
        Rapid assay of intrinsic radiosensitivity based on apoptosis in human CD4 and CD8 T-lymphocytes.
        Int J Radiat Oncol Biol Phys. 1997; 38: 429-440
        • Ozsahin M.
        • Crompton N.E.
        • Gourgou S.
        • et al.
        CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity.
        Clin Cancer Res. 2005; 11: 7426-7433
        • Azria D.
        • Gourgou S.
        • Sozzi W.J.
        • et al.
        Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients.
        Br J Cancer. 2004; 91: 1251-1260
        • Rigaud O.
        • Guedeney G.
        • Duranton I.
        • et al.
        Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. II. Alteration of DNA repair and chromosome radiosensitivity.
        Mutat Res. 1990; 242: 25-35
        • Miller B.
        • Potter-Locher F.
        • Seelbach A.
        • et al.
        Evaluation of the in vitro micronucleus test as an alternative to the in vitro chromosomal aberration assay.
        Mutat Res. 1998; 410: 81-116
        • Fenech M.
        The cytokinesis-block micronucleus technique and its application to genotoxicity studies in human populations.
        Environ Health Perspect. 1993; 101: 101-107
        • Muller W.U.
        • Streffer C.
        • Wuttke K.
        Micronucleus determination as a means to assess radiation exposure.
        Stem Cells. 1995; 13: 199-206
        • Muller W.U.
        • Nusse M.
        • Miller B.M.
        • et al.
        Micronuclei.
        Mutat Res. 1996; 366: 163-169
        • Geard C.R.
        • Chen C.Y.
        Micronuclei and clonogenicity following low- and high-dose-rate gamma irradiation of normal human fibroblasts.
        Radiat Res. 1990; 124: S56-S61
        • Shibamoto Y.
        • Streffer C.
        • Fuhrmann C.
        • et al.
        Tumor radiosensitivity prediction by the cytokinesis-block micronucleus assay.
        Radiat Res. 1991; 128: 293-300
        • Champion A.R.
        • Hanson J.A.
        • Venables S.E.
        • et al.
        Determination of radiosensitivity in established and primary squamous cell carcinoma cultures using the micronucleus assay.
        Eur J Cancer. 1997; 33: 453-462
        • Twardella D.
        • Chang-Claude J.
        Studies on radiosensitivity from an epidemiological point of view–overview of methods and results.
        Radiother Oncol. 2002; 62: 249-260
        • Alizadeh A.A.
        • Eisen M.B.
        • Davis R.E.
        • et al.
        Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.
        Nature. 2000; 403: 503-511
        • Pomeroy S.L.
        • Tamayo P.
        • Gaasenbeek M.
        • et al.
        Prediction of central nervous system embryonal tumour outcome based on gene expression.
        Nature. 2002; 415: 436-442
        • van ’t Veer L.J.
        • Dai H.
        • van de Vijver M.J.
        • et al.
        Gene expression profiling predicts clinical outcome of breast cancer.
        Nature. 2002; 415: 530-536
        • Torres-Roca J.F.
        • Eschrich S.
        • Zhao H.
        • et al.
        Prediction of radiation sensitivity using a gene expression classifier.
        Cancer Res. 2005; 65: 7169-7176
        • Sotiriou C.
        • Lothaire P.
        • Dequanter D.
        • et al.
        Molecular profiling of head and neck tumors.
        Curr Opin Oncol. 2004; 16: 211-214
        • Lonning P.E.
        • Sorlie T.
        • Borresen-Dale A.L.
        Genomics in breast cancer-therapeutic implications.
        Nat Clin Pract Oncol. 2005; 2: 26-33
        • Quarmby S.
        • West C.
        • Magee B.
        • et al.
        Differential expression of cytokine genes in fibroblasts derived from skin biopsies of patients who developed minimal or severe normal tissue damage after radiotherapy.
        Radiat Res. 2002; 157: 243-248
        • Ismail S.M.
        • Buchholz T.A.
        • Story M.
        • et al.
        Radiosensitivity is predicted by DNA end-binding complex density, but not by nuclear levels of band components.
        Radiother Oncol. 2004; 72: 325-332
        • West C.M.
        • McKay M.J.
        • Holscher T.
        • et al.
        Molecular markers predicting radiotherapy response.
        Int J Radiat Oncol Biol Phys. 2005; 62: 1264-1273
        • Iwakawa M.
        • Imai T.
        • Harada Y.
        • et al.
        [RadGenomics project].
        Nippon Igaku Hoshasen Gakkai Zasshi. 2002; 62 (in Japanese): 484-489
      1. Rosenstein BS. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer. The Fourth Era of Hope Meeting for the Department of Defense (DOD) Breast Cancer Research Program 2005; p. 62–17.

        • Holden C.
        Race and medicine.
        Science. 2003; 302: 594-596
        • Brookes A.J.
        The essence of SNPs.
        Gene. 1999; 234: 177-186
        • Shiloh Y.
        ATM and related protein kinases.
        Nat Rev Cancer. 2003; 3: 155-168
        • Savitsky K.
        • Bar-Shira A.
        • Gilad S.
        • et al.
        A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
        Science. 1995; 268: 1749-1753
        • Lavin M.F.
        • Birrell G.
        • Chen P.
        • et al.
        ATM signaling and genomic stability in response to DNA damage.
        Mutat Res. 2005; 569: 123-132
        • McKinnon P.J.
        ATM and ataxia telangiectasia.
        EMBO Rep. 2004; 5: 772-776
        • Gotoff S.P.
        • Amirmokri E.
        • Liebner E.J.
        Ataxia telangiectasia. Neoplasia, untoward response to x-irradiation, and tuberous sclerosis.
        Am J Dis Child. 1967; 114: 617-625
        • Morgan J.L.
        • Holcomb T.M.
        • Morrissey R.W.
        Radiation reaction in ataxia telangiectasia.
        Am J Dis Child. 1968; 116: 557-558
        • Pandita T.K.
        • Hittelman W.N.
        Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cells.
        Mutat Res. 1994; 310: 1-13
        • Parshad R.
        • Sanford K.K.
        • Jones G.M.
        • et al.
        G2 chromosomal radiosensitivity of ataxia-telangiectasia heterozygotes.
        Cancer Genet Cytogenet. 1985; 14: 163-168
        • Shiloh Y.
        • Parshad R.
        • Sanford K.K.
        • et al.
        Carrier detection in ataxia-telangiectasia.
        Lancet. 1986; 1: 689-690
        • Sanford K.K.
        • Parshad R.
        • Price F.M.
        • et al.
        Enhanced chromatid damage in blood lymphocytes after G2 phase x irradiation, a marker of the ataxia-telangiectasia gene.
        J Natl Cancer Inst. 1990; 82: 1050-1054
        • Paterson M.C.
        • MacFarlane S.J.
        • Gentner N.E.
        • et al.
        Cellular hypersensitivity to chronic gamma-radiation in cultured fibroblasts from ataxia-telangiectasia heterozygotes.
        Kroc Found Ser. 1985; 19: 73-87
        • Weeks D.E.
        • Paterson M.C.
        • Lange K.
        • et al.
        Assessment of chronic gamma radiosensitivity as an in vitro assay for heterozygote identification of ataxia-telangiectasia.
        Radiat Res. 1991; 128: 90-99
        • Appleby J.M.
        • Barber J.B.
        • Levine E.
        • et al.
        Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
        Br J Cancer. 1997; 76: 1546-1549
        • Ramsay J.
        • Birrell G.
        • Lavin M.
        Testing for mutations of the ataxia telangiectasia gene in radiosensitive breast cancer patients.
        Radiother Oncol. 1998; 47: 125-128
        • Clarke R.A.
        • Goozee G.R.
        • Birrell G.
        • et al.
        Absence of ATM truncations in patients with severe acute radiation reactions.
        Int J Radiat Oncol Biol Phys. 1998; 41: 1021-1027
        • Oppitz U.
        • Bernthaler U.
        • Schindler D.
        • et al.
        Sequence analysis of the ATM gene in 20 patients with RTOG grade 3 or 4 acute and/or late tissue radiation side effects.
        Int J Radiat Oncol Biol Phys. 1999; 44: 981-988
        • Weissberg J.B.
        • Huang D.D.
        • Swift M.
        Radiosensitivity of normal tissues in ataxia-telangiectasia heterozygotes.
        Int J Radiat Oncol Biol Phys. 1998; 42: 1133-1136
        • Concannon P.
        • Gatti R.A.
        Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia.
        Hum Mutat. 1997; 10: 100-107
        • Gilad S.
        • Khosravi R.
        • Shkedy D.
        • et al.
        Predominance of null mutations in ataxia-telangiectasia.
        Hum Mol Genet. 1996; 5: 433-439
        • Telatar M.
        • Teraoka S.
        • Wang Z.
        • et al.
        Ataxia-telangiectasia.
        Am J Hum Genet. 1998; 62: 86-97
        • Iannuzzi C.M.
        • Atencio D.P.
        • Green S.
        • et al.
        ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects.
        Int J Radiat Oncol Biol Phys. 2002; 52: 606-613
        • Andreassen C.N.
        • Overgaard J.
        • Alsner J.
        • et al.
        ATM sequence variants and risk of radiation-induced subcutaneous fibrosis after post-mastectomy radiotherapy.
        Int J Radiat Oncol Biol Physics. 2006; 64: 776-783
        • Angele S.
        • Romestaing P.
        • Moullan N.
        • et al.
        ATM haplotypes and cellular response to DNA damage.
        Cancer Res. 2003; 63: 8717-8725
        • Andreassen C.N.
        • Alsner J.
        • Overgaard J.
        • et al.
        TGFB1 polymorphisms are associated with risk of late normal tissue complications in the breast after radiotherapy for early breast cancer.
        Radiother Oncol. 2005; 75: 18-21
        • Hall E.J.
        • Schiff P.B.
        • Hanks G.E.
        • et al.
        A preliminary report.
        Cancer J Sci Am. 1998; 4: 385-389
        • Cesaretti J.A.
        • Stock R.G.
        • Lehrer S.
        • et al.
        ATM sequence variants are predictive of adverse radiotherapy response among patients treated for prostate cancer.
        Int J Radiat Oncol Biol Phys. 2005; 61: 196-202
        • Martin M.
        • Lefaix J.
        • Delanian S.
        TGF-beta1 and radiation fibrosis.
        Int J Radiat Oncol Biol Phys. 2000; 47: 277-290
        • Marsin S.
        • Vidal A.E.
        • Sossou M.
        • et al.
        Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1.
        J Biol Chem. 2003; 278: 44068-44074
        • Thompson L.H.
        • West M.G.
        XRCC1 keeps DNA from getting stranded.
        Mutat Res. 2000; 459: 1-18
        • Liu Y.
        • Masson J.Y.
        • Shah R.
        • et al.
        RAD51C is required for Holliday junction processing in mammalian cells.
        Science. 2004; 303: 243-246
        • Zelko I.N.
        • Mariani T.J.
        • Folz R.J.
        Superoxide dismutase multigene family.
        Free Radic Biol Med. 2002; 33: 337-349
        • McKay M.J.
        • Troelstra C.
        • van der Spek P.
        • et al.
        Sequence conservation of the rad21 Schizosaccharomyces pombe DNA double-strand break repair gene in human and mouse.
        Genomics. 1996; 36: 305-315
        • Birkenbihl R.P.
        • Subramani S.
        Cloning and characterization of rad21 an essential gene of Schizosaccharomyces pombe involved in DNA double-strand-break repair.
        Nucleic Acids Res. 1992; 20: 6605-6611
        • Pati D.
        • Zhang N.
        • Plon S.E.
        Linking sister chromatid cohesion and apoptosis.
        Mol Cell Biol. 2002; 22: 8267-8277
        • Quarmby S.
        • Fakhoury H.
        • Levine E.
        • et al.
        Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients.
        Int J Radiat Biol. 2003; 79: 137-143
        • Andreassen C.N.
        • Alsner J.
        • Overgaard M.
        • et al.
        Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes.
        Radiother Oncol. 2003; 69: 127-135
        • Moullan N.
        • Cox D.G.
        • Angele S.
        • et al.
        Polymorphisms in the DNA repair gene XRCC1, breast cancer risk, and response to radiotherapy.
        Cancer Epidemiol Biomarkers Prev. 2003; 12: 1168-1174
        • Severin D.M.
        • Leong T.
        • Cassidy B.
        • et al.
        Novel DNA sequence variants in the hHR21 DNA repair gene in radiosensitive cancer patients.
        Int J Radiat Oncol Biol Phys. 2001; 50: 1323-1331
        • Cavalli-Sforza L.L.
        The Human Genome Diversity Project.
        Nat Rev Genet. 2005; 6: 333-340
        • Lee J.E.
        • Choi J.H.
        • Lee J.H.
        • et al.
        Gene SNPs and mutations in clinical genetic testing.
        Mutat Res. 2005; 573: 195-204
        • Mehrian-Shai R.
        • Reichardt J.K.
        A renaissance of “biochemical genetics”? SNPs, haplotypes, function, and complex diseases.
        Mol Genet Metab. 2004; 83: 47-50
        • Erichsen H.C.
        • Chanock S.J.
        SNPs in cancer research and treatment.
        Br J Cancer. 2004; 90: 747-751
        • Lawrence R.W.
        • Evans D.M.
        • Cardon L.R.
        Prospects and pitfalls in whole genome association studies.
        Philos Trans R Soc Lond B Biol Sci. 2005; 360: 1589-1595
        • Newton-Cheh C.
        • Hirschhorn J.N.
        Genetic association studies of complex traits.
        Mutat Res. 2005; 573: 54-69
        • Hirschhorn J.N.
        Genetic approaches to studying common diseases and complex traits.
        Pediatr Res. 2005; 57: 74R-77R
        • Hirschhorn J.N.
        • Daly M.J.
        Genome-wide association studies for common diseases and complex traits.
        Nat Rev Genet. 2005; 6: 95-108
        • Halushka M.K.
        • Fan J.B.
        • Bentley K.
        • et al.
        Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.
        Nat Genet. 1999; 22: 239-247
        • Doris P.A.
        Hypertension genetics, single nucleotide polymorphisms, and the common disease:common variant hypothesis.
        Hypertension. 2002; 39: 323-331
        • Pritchard J.K.
        Are rare variants responsible for susceptibility to complex diseases?.
        Am J Hum Genet. 2001; 69: 124-137
        • Su Y.
        • Swift M.
        Outcomes of adjuvant radiation therapy for breast cancer in women with ataxia-telangiectasia mutations.
        J Am Med Assoc. 2001; 286: 2233-2234
        • Bremer M.
        • Klopper K.
        • Yamini P.
        • et al.
        Clinical radiosensitivity in breast cancer patients carrying pathogenic ATM gene mutations.
        Radiother Oncol. 2003; 69: 155-160
        • Gatti R.A.
        • Tward A.
        • Concannon P.
        Cancer risk in ATM heterozygotes.
        Mol Genet Metab. 1999; 68: 419-423
        • Huber C.G.
        • Oefner P.J.
        • Bonn G.K.
        High-resolution liquid chromatography of oligonucleotides on nonporous alkylated styrene-divinylbenzene copolymers.
        Anal Biochem. 1993; 212: 351-358
        • Kuklin A.
        • Munson K.
        • Gjerde D.
        • et al.
        Detection of single-nucleotide polymorphisms with the WAVE DNA fragment analysis system.
        Genet Test. 1997; 1: 201-206
        • Varghese S.
        • Schmidt-Ullrich R.K.
        • Dritschilo A.
        • et al.
        Enhanced radiation late effects and cellular radiation sensitivity in an ATM heterozygous breast cancer patient.
        Radiat Oncol Investig. 1999; 7: 231-237
        • O’Donovan M.C.
        • Oefner P.J.
        • Roberts S.C.
        • et al.
        Blind analysis of denaturing high-performance liquid chromatography as a tool for mutation detection.
        Genomics. 1998; 52: 44-49
        • Liu W.
        • Smith D.I.
        • Rechtzigel K.J.
        • et al.
        Denaturing high performance liquid chromatography (DHPLC) used in the detection of germline and somatic mutations.
        Nucleic Acids Res. 1998; 26: 1396-1400
        • Arnold N.
        • Gross E.
        • Schwarz-Boeger U.
        • et al.
        A highly sensitive, fast, and economical technique for mutation analysis in hereditary breast and ovarian cancers.
        Hum Mutat. 1999; 14: 333-339
        • Choy Y.S.
        • Dabora S.L.
        • Hall F.
        • et al.
        Superiority of denaturing high performance liquid chromatography over single-stranded conformation and conformation-sensitive gel electrophoresis for mutation detection in TSC2.
        Ann Hum Genet. 1999; 63: 383-391
        • Jones A.C.
        • Austin J.
        • Hansen N.
        • et al.
        Optimal temperature selection for mutation detection by denaturing HPLC and comparison to single-stranded conformation polymorphism and heteroduplex analysis.
        Clin Chem. 1999; 45: 1133-1140
        • Wagner T.
        • Stoppa-Lyonnet D.
        • Fleischmann E.
        • et al.
        Denaturing high-performance liquid chromatography detects reliably BRCA1 and BRCA2 mutations.
        Genomics. 1999; 62: 369-376
        • Gross E.
        • Arnold N.
        • Pfeifer K.
        • et al.
        Identification of specific BRCA1 and BRCA2 variants by DHPLC.
        Hum Mutat. 2000; 16: 345-353
        • Nickerson M.L.
        • Weirich G.
        • Zbar B.
        • et al.
        Signature-based analysis of MET proto-oncogene mutations using DHPLC.
        Hum Mutat. 2000; 16: 68-76
        • Bernstein J.L.
        • Teraoka S.
        • Haile R.W.
        • et al.
        Designing and implementing quality control for multi-center screening of mutations in the ATM gene among women with breast cancer.
        Hum Mutat. 2003; 21: 542-550
        • Qiu P.
        • Shandilya H.
        • D’Alessio J.M.
        • et al.
        Mutation detection using Surveyor nuclease.
        Biotechniques. 2004; 36: 702-707
        • Bannwarth S.
        • Procaccio V.
        • Paquis-Flucklinger V.
        Surveyor Nuclease.
        Hum Mutat. 2005; 25: 575-582
        • Shi R.
        • Otomo K.
        • Yamada H.
        Temperature-mediated heteroduplex analysis for the detection of drug-resistant gene mutations in clinical isolates of Mycobacterium tuberculosis by denaturing HPLC, SURVEYOR nuclease.
        Microbes Infect. 2006; 8: 125-135
        • Janne P.A.
        • Borras A.M.
        • Kuang Y.
        • et al.
        A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening.
        Clin Cancer Res. 2006; 12: 751-758
        • Shendure J.
        • Porreca G.J.
        • Reppas N.B.
        • et al.
        Accurate multiplex polony sequencing of an evolved bacterial genome.
        Science. 2005;
        • Pennisi E.
        Biochemistry. Cut-rate genomes on the horizon?.
        Science. 2005; 309: 862

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