Xeroderma Pigmentosum and Medulloblastoma: Chromosomal Damage to Lymphocytes during Radiotherapy

Giannelli, Flavio; Avery, J; Polani, P. E.; Terrell, Catherine E.; Giammusso, V.

doi:10.2307/3575764

Cited by 14 publications

(10 citation statements)

References 22 publications

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“…These include brain medulloblastoma (Giannelli et al 1981), glioblastoma, spinal cord astrocytoma (DiGiovanna et al 1998) and Schwannoma. These are not sunlight exposed tissues and the relationship of these cancers to DNA damage is not known.…”

Section: What Have We Learned About Xp and What Has Xp Taught Us Aboumentioning

confidence: 99%

“…Most of the X-ray damage is different and the X-ray repair systems are normal in XP cells. In fact, patients with XP who develop inoperable eye or internal tumors such as brain or spinal cord tumors have been treated with high dose x-irradiation as therapy and tolerated the treatment well (Grier 1919; Giannelli et al 1981; DiGiovanna et al 1998). This is in contrast to patients who are hypersensitive to x-irradiation, such as patients with the nevoid basal cell carcinoma syndrome (NBCC).…”

Section: What Have We Learned About Xp and What Has Xp Taught Us Aboumentioning

confidence: 99%

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Shining a Light on Xeroderma Pigmentosum

DiGiovanna

Kraemer

2012

Journal of Investigative Dermatology

460

503

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Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder of DNA repair characterized by sun sensitivity and ultraviolet (UV) induced skin and mucous membrane cancers. Described in 1874 by Moriz Kaposi in Vienna, nearly 100 years later James Cleaver in San Francisco reported defective DNA repair in XP cells. This eventually provided the basis for a mechanistic link between sun exposure, DNA damage, somatic mutations and skin cancer. XP cells were found to have defects in 7 of the proteins of the nucleotide excision repair pathway and in DNA polymerase eta. XP cells are hypersensitive to killing by UV and XP cancers have characteristic “UV signature” mutations. Clinical studies at NIH found a nearly 10,000-fold increase in skin cancer in XP patients under age 20 years demonstrating the substantial importance of DNA repair in cancer prevention in the general population. About 25 % of XP patients have progressive neurological degeneration with progressive loss of neurons, probably from DNA damage induced by oxidative metabolism which kills non-dividing cells in the nervous system. Interestingly, patients with another disorder, trichothiodystrophy have defects in some of the same genes as XP but they have primary developmental abnormalities without an increase in skin cancer.

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Section: What Have We Learned About Xp and What Has Xp Taught Us Aboumentioning

confidence: 99%

Section: What Have We Learned About Xp and What Has Xp Taught Us Aboumentioning

confidence: 99%

Shining a Light on Xeroderma Pigmentosum

DiGiovanna

Kraemer

2012

Journal of Investigative Dermatology

460

503

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“…Increased development of malignancies in irradiated skin was not noted in any of the previous reports of RT in XP patients, with a mean follow-up period of 8 years (range 3 months to >25 years) [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. Suboptimal cure rates and potential difficulties with future surgical procedures in previously irradiated skin as well as the risk of radiation-induced malignancies later in life limit the use of RT as a primary treatment modality for skin cancers in individuals with and without XP (especially younger patients) [38].…”

Section: Discussionmentioning

confidence: 98%

“…Including our cases, there have been at least 18 detailed descriptions in the literature of RT for cutaneous (13 cases) and extracutaneous (5 cases) malignancies in XP patients [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. Characteristics of the patients, neoplasms, treatment protocols, complications and outcomes are presented in table 1.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the frequency of aggressive cutaneous and extracutaneous malignancies, there have been relatively few reports of RT in individuals with XP [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. Most of these were in journals focused on radiation medicine or oncology, with rare documentation in the dermatologic literature of RT in patients with XP [13,16].…”

Section: Introductionmentioning

confidence: 99%

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Radiation Therapy for High-Risk Squamous Cell Carcinomas in Patients with Xeroderma Pigmentosum: Report of Two Cases and Review of the Literature

Schaffer

Orlow²

2011

Dermatology

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Radiation therapy (RT) represents an important adjuvant treatment modality for high-risk squamous cell carcinomas (SCCs). Despite the frequency of aggressive cutaneous and extracutaneous malignancies, there have been relatively few reports of RT in individuals with xeroderma pigmentosum (XP). We describe 2 adolescent boys with XP and high-risk SCCs of the skin that were treated with standard RT regimens without acute or chronic complications. After follow-up periods of 2 and 7 years, both of these patients had developed fewer skin cancers on the treated side of the face. A review of reported cases revealed that XP patients generally have normal cellular and clinical responses to ionizing radiation, which reflects the specificity of their nucleotide excision repair defect for ultraviolet radiation-induced DNA damage.

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