Cardiac fibroma is more commonly encountered in patients with Gorlin syndrome than the general population. Mutations of the tumor suppressor gene PTCH1 localized to 9q22.3 are the underlying cause of Gorlin syndrome. In this study, homozygous or heterozygous loss of the PTCH1 locus was identified in three nonsyndromic cardiac fibromas. These data support a somatic role of the PTCH1 tumor suppressor gene in sporadic cardiac fibroma.
Cardiac fibroma is a rare benign tumor that is poorly characterized genetically. Cardiac fibroma 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.
Conventional cytogenetic analysis was performed on a peripheral blood and a cardiac fibroma sample from a 2-week-old male. In addition, 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 YAC probe 891G1 and on representative paraffin-embedded tissue sections of two additional cardiac fibromas (one arising in a 2-month-old female and the other in a 13-week-old male). None of the patients had Gorlin syndrome.
Karyotypically, the following abnormal chromosomal complement was detected in the 2-week-old male’s cardiac fibroma: 46,XY,del(9)(q22q34). FISH studies revealed homozygous loss of the PTCH1 locus in the cytogenetically analyzed cardiac fibroma and in the cardiac fibroma arising in the 13-week-old male. Heterozygous loss of this locus was identified in the remaining cardiac fibroma 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.
These data support a tumor suppressor gene role for PTCH1 in nonsyndromic or sporadic cardiac fibromas.
Keywords: Cardiac fibroma, Gorlin syndrome, PTCH1 gene