Few FH mutations in sporadic counterparts of tumor types observed in hereditary leiomyomatosis and renal cell cancer families.
Loss of function mutations in the fumarate hydratase (fumarase, FH) gene were recently identified as the cause for dominantly inherited uterine and cutaneous leiomyomas and renal cell cancer. To further evaluate the role of FH in tumorigenesis, we screened FH mutations from tumor types seen in hereditary leiomyomatosis and renal cell cancer mutation carriers-41 uterine and 10 cutaneous leiomyomas, 52 renal cell carcinomas, 53 sarcomas, 29 prostate carcinomas, and 15 lobular breast carcinomas. Few mutations were detected. Biallelic inactivation of FH was found in one uterine leiomyosarcoma, one cutaneous leiomyoma, and one soft tissue sarcoma. Whereas the two former lesions were shown to originate from a germ-line mutation, the soft tissue sarcoma is to our knowledge the first example of purely somatic inactivation of FH in tumors.
Department of Medical Genetics, Biomedicum Helsinki or Haartman Institute, University of Helsinki, FIN-00014 Helsinki, Finland.
Maija
M
Kiuru
Rainer
R
Lehtonen
Johanna
J
Arola
Reijo
R
Salovaara
Heikki
H
Järvinen
Kristiina
K
Aittomäki
Jari
J
Sjöberg
Tapio
T
Visakorpi
Sakari
S
Knuutila
Jorma
J
Isola
Brett
B
Delahunt
Riitta
R
Herva
Virpi
V
Launonen
Auli
A
Karhu
Lauri A
LA
Aaltonen
D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005649:Fumarate Hydratase / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics*; D007889:Leiomyoma / Q000201:enzymology / Q000235:genetics*; D007890:Leiomyosarcoma / Q000201:enzymology / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics*; D014594:Uterine Neoplasms / Q000201:enzymology / Q000235:genetics*
D005649:Fumarate Hydratase