Hypothesis: Possible role of retinoic acid therapy in patients with biallelic mismatch repair gene defects.
A boy showing symptoms of a Turcot-like childhood cancer syndrome together with stigmata of neurofibromatosis type I is reported. His brother suffers from an infantile myofibromatosis, and a sister died of glioblastoma at age 7. Another 7-year-old brother is so far clinically unaffected. The parents are consanguineous. Molecular diagnosis in the index patient revealed a constitutional homozygous mutation of the mismatch repair gene PMS2. The patient was in remission of his glioblastoma (WHO grade IV) after multimodal treatment followed by retinoic acid chemoprevention for 7 years. After discontinuation of retinoic acid medication, he developed a relapse of his brain tumour together with the simultaneous occurrence of three other different HNPCC-related carcinomas. We think that retinoic acid might have provided an effective chemoprevention in this patient with homozygous mismatch repair gene defect. We propose to take a retinoic acid chemoprevention into account in children with proven biallelic PMS2 mismatch repair mutations being at highest risk concerning the development of a malignancy.
Gottschling
Sven
S
Department of Pediatric Hematology and Oncology Saarland University, University Children's Hospital, Homburg, Germany. kisgot@uniklinik-saarland.de
Reinhard
Harald
H
Pagenstecher
Constanze
C
Krüger
Stefan
S
Raedle
Jochen
J
Plotz
Guido
G
Henn
Wolfram
W
Buettner
Reinhard
R
Meyer
Sascha
S
Graf
Norbert
N
D018256:Adenomatous Polyps / Q000235:genetics / Q000517:prevention & control; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000483:Alleles; D020137:Base Pair Mismatch; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control*; D002648:Child; D015179:Colorectal Neoplasms / Q000235:genetics / Q000517:prevention & control; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control*; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D000070976:Mismatch Repair Endonuclease PMS2; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D013577:Syndrome; D014212:Tretinoin / Q000627:therapeutic use*
D004268:DNA-Binding Proteins; D014212:Tretinoin; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes