The Principles of Clinical Cytogenetics - Extra Materials - Springer

436 Jonathan Fletcher
Fig. 6. Neuroblastoma metaphase cell with numerous double minute chromosomes of varying sizes (arrows).
tumor suppressor gene, INI1 (also known as SNF5 or SMARCB1), which encodes a protein involved
in chromatin remodeling (121,122). The rhabdoid tumor karyotypic profile is quite characteristic,
inasmuch as the chromosome 22 deletion is often the only detectable cytogenetic aberration, suggesting
that INI1 inactivation is a relatively early event in rhabdoid tumorigenesis. Additional evidence
of an essential tumorigenic role includes the finding of germline INI1 mutations in some individuals
with rhabdoid tumors (122,123) and the development of rhabdoid tumors in mice with inactivating
INI1 mutations (124).
Smooth Muscle Tumors
Malignant smooth muscle tumors (i.e., leiomyosarcomas) generally have complex karyotypes, but
the most consistent finding has been deletion of the short arm of chromosome 1 (125,126) (see Table 1).
The 1p deletion is not helpful diagnostically, because similar deletions are found in many of the
leiomyosarcoma mimics, including malignant fibrous histiocytoma, malignant peripheral nerve
sheath tumors, and gastrointestinal stromal tumors (126). The cytogenetic complexity in leiomyosarcomas
can be striking even in low-grade specimens (see Fig. 7) (127). Benign smooth muscle tumors
(leiomyomas), particularly those of uterine origin, contain various translocations and deletions, but
generally in the context of a simple karyotype. Approximately 50% of benign leiomyomas lack evident
cytogenetic aberrations.
Deletions of the long arm of chromosome 7 are found in 15–25% of uterine leiomyomas, whereas
trisomy 12 and rearrangements of the short arm of chromosome 6 are each found in approximately
10–15% of cases (128–130). However, the most distinctive cytogenetic abnormality in leiomyoma is
a translocation involving chromosomes 12 and 14 that is found in approximately 20% of uterine
cases. This translocation appears to induce overexpression of the HMGIC (high-mobility group IC)
gene on chromosome 12 by virtue of juxtaposition with the RAD51 (recombinational repair) gene on
chromosome 14 (131).