Loss of the PTCH1 gene locus in cardiac fibroma.
BACKGROUND
Cardiac fibroma (CF) is a rare benign tumor that is poorly characterized genetically. CF is more commonly encountered in patients with Gorlin syndrome (3%) than the general population. Mutations of the tumor suppressor gene PTCH1 are the underlying cause of Gorlin syndrome.


METHODS
Conventional cytogenetic analysis was performed on a peripheral blood and a CF sample from a 2-week-old male. In addition, fluorescence in situ hybridization (FISH) studies were performed to assess the copy number of the PTCH1 gene locus (9q22.3) on metaphase and interphase cells from these same specimens using yeast artificial protein (YAC) probe 891G1 and on representative paraffin-embedded tissue sections of two additional CFs (one arising in a 2-month-old female and the other in a 13-week-old male). None of the patients had Gorlin syndrome.


RESULTS
Karyotypically, the following abnormal chromosomal complement was detected in the 2-week-old male's CF: 46,XY,del(9)(q22q34)[15]. FISH studies revealed homozygous loss of the PTCH1 locus in the cytogenetically analyzed CF and in the CF arising in the 13-week-old male. Heterozygous loss of this locus was identified in the remaining CF from the 2-month-old female. A mutational mechanism other than deletion may be responsible for PTCH1 inactivation on the other locus in this latter patient. Conventional cytogenetic and FISH studies of the peripheral blood sample from the 2-week-old male were normal.


CONCLUSIONS
These data support a tumor suppressor gene role for PTCH1 in nonsyndromic or sporadic CFs.
Scanlan
David
D
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-8135, USA.
Radio
Stanley J
SJ
Nelson
Marilu
M
Zhou
Ming
M
Streblow
Renae
R
Prasad
Vinay
V
Reyes
Christine
C
Perry
Deborah
D
Fletcher
Scott
S
Bridge
Julia A
JA
D001478:Basal Cell Nevus Syndrome / Q000235:genetics; D002869:Chromosome Aberrations; D005260:Female; D005350:Fibroma / Q000235:genetics* / Q000473:pathology; D017353:Gene Deletion; D006338:Heart Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics*; D032681:Spectral Karyotyping
C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface