5726

TAS2R38

PTC|T2R38|T2R61;taste receptor, type 2, member 38;TAS2R38;taste receptor, type 2, member 38

PTC bitter taste receptor|taste receptor type 2 member 38|taste receptor type 2 member 61

7q34

protein-coding

Rhabdomyosarcomas are a heterogeneous group of malignant tumors and are the mostcommon soft-tissue sarcoma of childhood. Rhabdomyosarcomas resemble developing skeletal muscle, notably in their expression of the MRF family of transcription factors and the PAX3 and PAX7 genes. These PAX genes are also involved through specific translocations, t(2;13)(q35;q14) and variant t(1;13)(p36;q14) in the alveolar subtype, which result in PAX3-FKHR and PAX7-FKHR fusion genes, respectively. The fusion genes are thought critically to affect downstream targets of PAX3 and PAX7 or possibly have novel targets. Similar downstream changes may also be involved in embryonal and fusion gene negative cases. Genomic amplification of such genes as MYCN, MDM2, CDK4, and PAX7-FKHR is a feature mainly of the alveolar subtype, while specific chromosomal gains, including chromosomes 2, 8, 12, and 13, are associated with the embryonal subtype. Loss ofalleles and imprinting at 11p15.5 and disruption of genes such as IGF2, ATR, PTC, P16, and TP53 have also been implicated in rhabdomyosarcoma development. Whereasthere is now a realistic possibility of cure in the majority of cases, there remains a subset that is resistant to multimodality therapy, including high-dosechemotherapy. Characterization of the defining molecular features of tumors thatare likely to behave aggressively represents a particular challenge. Current research is leading toward a better understanding of rhabdomyosarcoma tumorigenesis, which may ultimately result in novel therapeutic strategies that increase the overall cure. Genes Chromosomes cancer 26:275-285, 1999.#CI- Copyright 1999 Wiley-Liss, Inc.

Brain tumors are among the most common forms of cancer in children and account for most cancer-related deaths in this age group. The incidence of brain tumors appears to be increasing in children, while therapeutic advances have been modest. Few genetic studies exist on pediatric brain tumors, in part because tissue from low-grade and brain stem tumors is not readily available, and also because individual centers have relatively few cases. Genetic changes in infiltrating astrocytomas involve genes in the p53 and RB pathways, and show alterations that are similar to infiltrating astrocytomas in adults. The PTC gene is mutated in a subgroup of medulloblastomas, and may lead to increased proliferation in granule cells that normally express this receptor. Further studies are needed to identify genetic alterations in pilocytic and low-grade astrocytomas, which account for 40% of brain tumors in children.

Recent molecular genetic investigations of primary cardiac tumors (myxomas, lipomas, rhabdomyomas, and fibromas) have provided insight into fundamental mechanisms of cardiac cell growth. Myxomas are the most common adult cardiac tumor, and familial cardiac myxomas are now appreciated to be caused by mutations in the PRKAR1alpha gene that encodes a regulatory subunit of protein kinase A. Cytogenetic studies have targeted candidate chromosomal loci that may be perturbed during cardiac lipoma pathogenesis. Rhabdomyomas, the most common pediatric cardiac neoplasm, are frequently associated with tuberous sclerosis, caused by mutations in the TSC-1 and TSC-2 genes. The study of Gorlin syndrome has shed light on the etiology of cardiac fibromas. This disorder is caused by mutation of the PTC gene, which regulates cell growth, commitment and differentiation. In the future, manipulation of PRKAR1alpha-, TSC-, and PTC-dependent pathways may foster new strategies to regenerate myocardium in theischemic or myopathic heart.