Genetic and Clinical Study of Patients With Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy - Full Text View

Purpose

RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer and may lead to both earlier detection and prevention of tumors.

PURPOSE: Clinical trial to study the genetic and clinical features of patients who have xeroderma pigmentosum, Cockayne syndrome, the xeroderma pigmentosum/Cockayne syndrome complex, or trichothiodystrophy.

Condition	Intervention
Head and Neck Cancer Intraocular Melanoma Melanoma (Skin) Non-Melanomatous Skin Cancer Precancerous/Nonmalignant Condition	Procedure: DNA ploidy analysis Procedure: mutation analysis

Genetics Home Reference related topics:

Cockayne syndrome familial encephalopathy with neuroserpin inclusion bodies Opitz G/BBB syndrome pseudoachondroplasia retinoblastoma

MedlinePlus related topics:

Cancer Head and Neck Cancer Melanoma Skin Cancer

U.S. FDA Resources

Study Type:	Observational

Official Title:	Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	250
Study Start Date:	June 2000

Detailed Description:

OBJECTIVES:

Identify patients or confirm suspected cases of xeroderma pigmentosum (XP), Cockayne syndrome (CS), XP/CS, or trichothiodystrophy (TTD).
Document presence or absence of cancers (skin, eye, tongue, or internal) in these patients.
Document atypical features or unusual environmental exposures of these patients.
Examine tissue (skin, blood, hair, or buccal swabs) from these patients and their first degree relatives for DNA repair and genetic analysis.
Identify molecular defects in the DNA repair genes in cells from these patients and correlate the defects with clinical features.
Follow the clinical course of selected patients.

OUTLINE: Patients are evaluated initially by phone, followed by a complete history and physical exam, including appropriate clinical and laboratory tests.

Tissue (skin, blood, buccal swabs, or hair) is obtained for laboratory studies of the effects of DNA damage, measurement of DNA repair, genetic analysis of DNA, and/or assessment of immunologic abnormalities.

If malignancies are detected during examinations and tissue collections, patients are referred for treatment. Genetic counseling is also available.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Clinical documentation of the typical features of xeroderma pigmentosum (XP), Cockayne syndrome (CS), the XP/CS complex, or trichothiodystrophy OR
Laboratory documentation of defective DNA repair OR
Suggestive clinical features of one of these diseases OR
First degree family member or relative of affected patient
Must be willing or able to provide tissue sample (skin, blood, buccal cells, or hair) for laboratory studies

PATIENT CHARACTERISTICS:

Age:

Any age

Performance status:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004044

Locations


United States, Maryland
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
	Bethesda, Maryland, United States, 20892-1182
	Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Israel
	Sackler Faculty of Medicine	Recruiting
	Tel-Aviv, Israel, 69978
	Contact: Hanoch Slor, MD 972-3-545-9657

Turkey
	Inonu University School of Medicine	Recruiting
	Malatya, Turkey
	Contact: Engin Gozukara, PhD, MD 90-422-341-0045
	Yuzuncu Yil University School of Medicine	Recruiting
	Van, Turkey, 65200
	Contact: Ahmet Metin, MD 90-432-216-7325

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Study Chair:	Kenneth H. Kraemer, MD	NCI - Basic Research Laboratory

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

Khan SG, Oh KS, Shahlavi T, Ueda T, Busch DB, Inui H, Emmert S, Imoto K, Muniz-Medina V, Baker CC, DiGiovanna JJ, Schmidt D, Khadavi A, Metin A, Gozukara E, Slor H, Sarasin A, Kraemer KH. Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients. Carcinogenesis. 2006 Jan;27(1):84-94. Epub 2005 Aug 4.

Liang C, Kraemer KH, Morris A, Schiffmann R, Price VH, Menefee E, DiGiovanna JJ. Characterization of tiger-tail banding and hair shaft abnormalities in trichothiodystrophy. J Am Acad Dermatol. 2005 Feb;52(2):224-32.

Khan SG, Metin A, Gozukara E, Inui H, Shahlavi T, Muniz-Medina V, Baker CC, Ueda T, Aiken JR, Schneider TD, Kraemer KH. Two essential splice lariat branchpoint sequences in one intron in a xeroderma pigmentosum DNA repair gene: mutations result in reduced XPC mRNA levels that correlate with cancer risk. Hum Mol Genet. 2004 Feb 1;13(3):343-52. Epub 2003 Dec 8.

Khan S, Shahlavi T, Busch DB: Identification of XP-C heterozygotes using real-time quantitative reverse transcriptase-PCR: a novel approach to study the cancer susceptibility in XP-C gene carriers. [Abstract] The Fourth Joint Meeting of the European Society for Dermatology Research (ESDR), the Japanese Society for Investigative Dermatology (JSID), and the Society for Investigative Dermatology (SID), 30 April - 4 May, Miami, Florida. A-0647, 100, 2003.

Liang C, Price V, Kraemer KH: Tiger tail banding and hair shaft abnormalities in trichothiodystrophy and other hair disorders. [Abstract] The Fourth Joint Meeting of the European Society for Dermatology Research (ESDR), the Japanese Society for Investigative Dermatology (JSID), and the Society for Investigative Dermatology (SID), 30 April - 4 May, Miami, Florida. A-0792, 107, 2003.

Ueda T, Khan SG, Shahlavi T: Rapid RFLP detection of mutations and functional alterations in the human XPD DNA repair gene. [Abstract] The Fourth Joint Meeting of the European Society for Dermatology Research (ESDR), the Japanese Society for Investigative Dermatology (JSID), and the Society for Investigative Dermatology (SID), 30 April - 4 May, Miami, Florida. A-0644, 100, 2003.

Emmert S, Slor H, Busch DB, Batko S, Albert RB, Coleman D, Khan SG, Abu-Libdeh B, DiGiovanna JJ, Cunningham BB, Lee MM, Crollick J, Inui H, Ueda T, Hedayati M, Grossman L, Shahlavi T, Cleaver JE, Kraemer KH. Relationship of neurologic degeneration to genotype in three xeroderma pigmentosum group G patients. J Invest Dermatol. 2002 Jun;118(6):972-82. Erratum in: J Invest Dermatol. 2003 Jan;120(1):173.

Yavuz S, Yavuz AS, Kraemer KH, Lipsky PE. The role of polymerase eta in somatic hypermutation determined by analysis of mutations in a patient with xeroderma pigmentosum variant. J Immunol. 2002 Oct 1;169(7):3825-30.

Broughton BC, Berneburg M, Fawcett H, Taylor EM, Arlett CF, Nardo T, Stefanini M, Menefee E, Price VH, Queille S, Sarasin A, Bohnert E, Krutmann J, Davidson R, Kraemer KH, Lehmann AR. Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene. Hum Mol Genet. 2001 Oct 15;10(22):2539-47.

Gozukara EM, Khan SG, Metin A, Emmert S, Busch DB, Shahlavi T, Coleman DM, Miller M, Chinsomboon N, Stefanini M, Kraemer KH. A stop codon in xeroderma pigmentosum group C families in Turkey and Italy: molecular genetic evidence for a common ancestor. J Invest Dermatol. 2001 Aug;117(2):197-204.

Lindenbaum Y, Dickson D, Rosenbaum P, Kraemer K, Robbins I, Rapin I. Xeroderma pigmentosum/cockayne syndrome complex: first neuropathological study and review of eight other cases. Eur J Paediatr Neurol. 2001;5(6):225-42. Review.

Zeng X, Winter DB, Kasmer C, Kraemer KH, Lehmann AR, Gearhart PJ. DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes. Nat Immunol. 2001 Jun;2(6):537-41.

Slor H, Batko S, Khan SG, Sobe T, Emmert S, Khadavi A, Frumkin A, Busch DB, Albert RB, Kraemer KH. Clinical, cellular, and molecular features of an Israeli xeroderma pigmentosum family with a frameshift mutation in the XPC gene: sun protection prolongs life. J Invest Dermatol. 2000 Dec;115(6):974-80.

Other Publications:

Bohr VA, Sander M, Kraemer KH. Rare diseases provide rare insights into DNA repair pathways, TFIIH, aging and cancer center. DNA Repair (Amst). 2005 Feb 3;4(2):293-302.

Terunuma A, Ye J, Emmert S, Khan SG, Kraemer KH, Vogel JC. Ultraviolet light selection assay to optimize oligonucleotide correction of mutations in endogenous xeroderma pigmentosum genes. Gene Ther. 2004 Dec;11(23):1729-34.

Khan SG, Muniz-Medina V, Shahlavi T, Baker CC, Inui H, Ueda T, Emmert S, Schneider TD, Kraemer KH. The human XPC DNA repair gene: arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function. Nucleic Acids Res. 2002 Aug 15;30(16):3624-31.

Robbins JH, Kraemer KH, Merchant SN, Brumback RA. Adult-onset xeroderma pigmentosum neurological disease--observations in an autopsy case. Clin Neuropathol. 2002 Jan-Feb;21(1):18-23.

Suzuki H, Kalair W, Shivji GM, Wang B, Toto P, Amerio P, Kraemer KH, Sauder DN. Impaired ultraviolet-B-induced cytokine induction in xeroderma pigmentosum fibroblasts. J Invest Dermatol. 2001 Nov;117(5):1151-5.

Khan SG, Metter EJ, Tarone RE, Bohr VA, Grossman L, Hedayati M, Bale SJ, Emmert S, Kraemer KH. A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. Carcinogenesis. 2000 Oct;21(10):1821-5.

Study ID Numbers:	CDR0000067084, NCI-99-C-0099
First Received:	December 10, 1999
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00004044
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

basal cell carcinoma of the skin

squamous cell carcinoma of the skin

actinic keratosis

iris melanoma

ciliary body and choroid melanoma, medium/large size

ciliary body and choroid melanoma, small size

extraocular extension melanoma

stage I melanoma

stage I squamous cell carcinoma of the lip and oral cavity

Study placed in the following topic categories:

Dwarfism

Keratosis

Photosensitivity Disorders

Precancerous Conditions

Squamous cell carcinoma

Neurodegenerative Diseases

Bone Diseases

Melanoma

Uveal melanoma

Cockayne's syndrome

Heredodegenerative Disorders, Nervous System

Musculoskeletal Diseases

Intraocular melanoma

Nevus, Pigmented

Neoplasms, Germ Cell and Embryonal

Trichothiodystrophy

Carcinoma, squamous cell

Bone Diseases, Developmental

Abnormalities, Multiple

Neuroepithelioma

Congenital Abnormalities

Skin Diseases, Genetic

Xeroderma Pigmentosum

Metabolic Diseases

Skin Diseases

Eye Neoplasms

Eye Diseases

Skin Abnormalities

Carcinoma, Basal Cell

Skin Neoplasms

Additional relevant MeSH terms:

Neoplasms

Neoplasms by Histologic Type

Neoplasms by Site

Pigmentation Disorders

Neoplasms, Nerve Tissue

DNA Repair-Deficiency Disorders

Nervous System Diseases

Nevi and Melanomas

ClinicalTrials.gov processed this record on September 05, 2008

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00004044