<b>RB1</b> 

Loss of a single copy of chromosome 13 in the general region of the RB1 gene was found in around 35% of sarcomas [8]. These abnormalities have been found in many types of sarcomas but were found most commonly in malignant fibrous histiocytoma, leiomyosarcomas, and rhabdomyosarcomas. 

<b>CDKN2</b> 

Recently homozygous deletion (loss of both gene copies) of the CDKN2 gene, which encodes p16, been reported in malignant peripheral nerve sheath tumors, rhabdomyosarcomas, and leiomyosarcomas [5]. In the same study, amplification and overexpression of the CDK4 and cyclin D1 genes were observed in some sarcomas. 

The latter observation agreed with an immunological study showing that the cyclin D1 protein level is elevated in up to 40% of soft tissue sarcomas [6] and with an early report of CDK4 gene amplification in a rhabdomyosarcoma [7]. 

Direct evidence that cyclin D1 can have a role in cell transformation is provided by experiments showing that overexpression of this gene can (1) confer transformed properties on established fibroblast lines and (2) cooperate with other protooncogenes, including activated RAS and MYC genes, to transform primary cells. The detection of CDK4 amplification and overexpression is of interest because of some cell types it has been proposed that overexpression of CDK4 protein my act by rendering cells insensitive to the CDK inhibitor protein p15 that is induced following exposure to transforming growth factor beta. If removal of the TGF-Beta control pathway acting through p15 is indeed important in sarcoma induction, then it should also be possible to find alterations of the p15 gene, and the results of such studies are awaited with interest. 

<b>P53</b> 

The p53 gene is located on a region of chromosome 17 that is frequently lost during tumor development, and the p53 allele that remains in these tumors usually contains point mutations. Loss of chromosome 17 and inactivating point mutations have frequently been observed in soft tissue sarcomas, particularly in malignant fibrous histiocytoma, rhabdomyosarcomas, and leiomyosarcomas [10-12]. However, in contrast to the results obtained with most other cancer types but in common with osteosarcoma and blast crisis chronic myeolgenous leukemia, homozygous deletion of the p53 gene was also frequently observed [13,14]. 

In a study involving 29 leiomyosarcoma revealed p53 overexpression in 17% of tumors and in this study all tumors overexpressing p53 protein were also shown to contain point mutations in the p53 gene [16]. 

<b>No problem with MDM2</b> 

A study [9] showed that 0 of 14 leiomyosarcomas had MDM2 gene amplification. 

<b>N-RAS</b> 

Activated N-RAS was detected in a leiomyosarcoma [15]. 