Abstract |
We investigated a radiotherapy-induced flare and subsequent clearance of skin lesions of a patient with the rare, dominantly inherited genodermatosis, Darier's disease (DD). The DD gene, ATP2A2, was recently isolated and shown to be a cation pump responsible for regulating intracellular calcium homeostasis. A severe exacerbation of Darier's skin lesions developed within the radiation field when 40 Gy of palliative thoracic external-beam radiation therapy and concurrent chemotherapy ( cisplatin and hydroxyurea) were delivered for non-small cell lung cancer. The DD lesions subsequently completely cleared from irradiated skin, as they did when a subsequent course of radiation alone was given for a loco-regional tumor recurrence. The two radiation therapy-treated areas of skin remained free from lesions of the skin disorder until the patient's death from progressive lung cancer 9 months later. The nucleotide sequence of the patient's ATP2A2 gene was determined by PCR-based cycle sequencing. We identified four nucleotide sequence variants in the ATP2A2 gene in this patient. Three were probable polymorphisms and the other appeared to be a novel disease-causing mutation (R751Q), situated in the transmembrane portion of the ATP2A2 protein. This finding confirmed the clinical diagnosis. Since epidermis turns over every 3-4 weeks, total and persistent clearance of the DD lesions by chemoradiotherapy suggests that this treatment induced sustained differentiation of the DD-affected skin by an unknown mechanism. Oncologists treating malignant disease in patients with DD should anticipate temporary deterioration in DD-involved irradiated skin. Radiation therapy has therapeutic potential in severe DD.
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Authors | M P Mac Manus, G Cavalleri, D L Ball, M Beasley, H Rotstein, M J McKay |
Journal | Radiation research
(Radiat Res)
Vol. 156
Issue 6
Pg. 724-30
(Dec 2001)
ISSN: 0033-7587 [Print] United States |
PMID | 11741496
(Publication Type: Case Reports, Journal Article)
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Chemical References |
- DNA Primers
- Sarcoplasmic Reticulum Calcium-Transporting ATPases
- ATP2A2 protein, human
- Calcium-Transporting ATPases
- Cisplatin
- Hydroxyurea
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Topics |
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Base Sequence
- Calcium-Transporting ATPases
(genetics)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, radiotherapy)
- Cell Differentiation
(radiation effects)
- Cisplatin
(administration & dosage)
- Combined Modality Therapy
- DNA Primers
- Darier Disease
(etiology, genetics, pathology)
- Epidermal Cells
- Epidermis
(radiation effects)
- Humans
- Hydroxyurea
(administration & dosage)
- Lung Neoplasms
(drug therapy, radiotherapy)
- Male
- Middle Aged
- Mutation
- Polymerase Chain Reaction
- Radiotherapy
(adverse effects)
- Sarcoplasmic Reticulum Calcium-Transporting ATPases
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