Light microscopy analysis of the skin and tumor obtained from the Fanconi patient.

<p>Immunohistochemical staining of RAD51 and 53BP1 (diaminobenzidine, brown) in atrophic and dysplastic epidermis as well as tumor specimens derived from the Fanconi patient. Compared with healthy control epidermis moderately or considerably increased RAD51 and 53BP1 expression in the proliferating zone attached to the basement membrane. Immunfluorescence staining of 53BP1 (green) reveals discrete nuclear foci in the proliferating cells of the epidermis, with increasing foci levels during tumor development. Original magnification, x600.</p

Foci kinetics measured in blood lymphocytes.

<p>Double-strand break repair kinetics of ATM^−/− homozygotes, AMT^+/− heterozygotes (A), and tumor-children (B) compared to healthy control-children (ATM^+/+) evaluated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time-points after irradiation. GRJN developing grade-4 toxicities during multimodality treatment for medulloblastoma and SBNE with FA suffering relapsing squamous cell carcinomas of the oral cavity revealed impaired DSB repair capacities. * significant difference to healthy control-children (p≤0.05).</p

Characteristics of the children with tumors.

<p>Abbreviations: TMZ: Temodal, CCNU: Lomustin, VP-16: Etoposid, MTX: Methotrexat, IFO: Ifosfamid, DOX: Doxorubicin, CPM: Cyclophosphamid, CDDP: Cisplatin, DACT: Actinomycin-D, TOPO: Topotecan, DNR: Daunorubicin, DTIC: Dacarbacin, CBDCA: Carboplatin, IDA: Idarubicin, ADR: Adriamycin, TRO: Trofosfamid, EPI: Epirubicin.</p

DNA damage foci in blood lymphocytes.

<p>Immunofluorescence double staining of 53BP1 (green) and pATM (red) in blood lymphocytes of healthy individuals (ATM^+/+) and ATM^−/− homozygotes, analysed 24 h after irradiation with 2Gy compared to un-irradiated control. Deoxyribonucleic acid was counterstained with 4′,6-diamidino-2-phenylindole (blue), and images were merged to determine co-localization (yellow). Original magnification, x600.</p

Electron microscopy analysis of the mucosa and tumor obtained from the Fanconi patient.

<p>TEM micrographs of double-labeling of pKu70 (10-nm beads) and p53BP1 (6-nm beads) at different magnifications (boxed regions are shown at higher magnifications in the following images). Co-localization of pKu70 and 53BP1 in electron-dense regions, reflecting actively processed DSBs in heterochromatin.</p

MR imaging documenting severe normal tissue toxicity or synchronous tumors in patients.

<p>(A) Cranial magnetic resonance imaging of the patient GRJN before (left panel) and after tumour resection and adjuvant radio-/chemotherapy (right panel). T1-weighted images acquired in sagittal and axial plane shows cerebral atrophy with enlargement of the ventricles after multifactorial leukencephalopathy. (B) Cranial magnetic resonance imaging of the patient SBNE before surgical tumor resection. T1-weighted images acquired in sagittal and axial plane reveal the squamous cell carcinoma (SCC) of the oral cavity (tumors marked by arrows).</p