Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP is located on chromosome 11p15.5 (ref. 2), a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a familial cancer syndrome, marking it a tumour suppressor candidate. Several types of childhood tumours including Wilm's tumour, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the Beckwith-Wiedemann syndrome has indicated maternal carriers as well as suggested a role in genomic imprinting. Here, as a first step towards elucidating the genesis of human cancers in this region, we showed that a mouse homologue of p57KIP2 is genomically imprinted. The paternally inherited allele is transcriptionally repressed and methylated. This murine gene maps to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2, H19 and Mash2 (refs 14-18).
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PMID:Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse. 755 Mar 51

Pediatricians are often the health care providers who first detect the signs and symptoms of childhood cancer. Although pediatric malignancies are rare diseases, early diagnosis is an important factor leading to high cure rates of many types of cancers including retinoblastomara, Wilms' tumor, hepatoblastoma, rhabdomyosarcoma. thyroid carcinoma, and other solid tumors. A number of familial cancer syndromes present with childhood cancers that can be recognized or diagnosed by pediatricians. The genetic origins of several syndromes have been elucidated. Genetic testing is not yet available for all of these inherited cancers. A frequently updated list of genetic tests is available at www.genetests.org. The ordering and interpreting of genetic tests, however, is often best done by trained genetic counselors. The pediatrician will play a vital on-going role in following the at-risk child. In many of syndromes discussed, the cost effectiveness of the tests as well as that of any potential intervention needs further study. The role of the subtle genetic polymorphisms in pediatric tumorigenesis. many more of which will undoubtedly be described in the coming years, has not yet been translated into defined needs for interventions. Perhaps in the future it will be possible to understand the additive effect of multiple genetic polymorphisms and to determine genetic profiles of high cancer risk. Until suitable interventions are established, however, the study of genetic variability and cancer will await practical significance. Undoubtedly other major important cancer genes are yet to be discovered and characterized. An additional challenge is the counseling and management of children and adults who have a strong family history of cancer yet who do not have a recognizable syndrome. The role of the primary pediatrician is to recognize the major cancer genetic syndromes, to make appropriate referrals for genetic counseling and testing when indicated, and to ensure that adequate screening tests are being done.
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PMID:Genetic predisposition and screening in pediatric cancer. 1258 Mar 71

We present three cases of pleuropulmonary blastoma (PPB) in Australian children. Each had a family history of childhood tumors which collectively included PPB, infant lung cyst, cystic nephroma, medullo-epithelioma and a Sertoli-Leydig ovarian tumor. Two of the patients also had additional malignancies: a concurrent bladder rhabdomyosarcoma and a post therapy non-PPB malignant lung tumor. In two cases, the family histories were elicited years after the PPB diagnosis. Archived pathology material allowed revision of pathologic diagnoses from decades earlier. These cases illustrate the importance of detailed inquiry into family medical history and the pleiotropy of the PPB-related familial cancer predisposition syndrome, which appears to result from heterozygous DICER1 mutations.
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PMID:Familial pleuropulmonary blastoma in Australia. 2098 96

The sonic hedgehog (SHH) signaling pathway has been shown to play important roles in embryogenesis, cell proliferation as well as in cell differentiation. It is aberrantly activated in various common cancers in adults, but also in pediatric neoplasms, such as rhabdomyosarcoma (RMS) and atypical teratoid/rhabdoid tumors (AT/RTs). Dysregulation and germline mutation in PATCHED1 (PTCH1), a receptor for SHH, is responsible for the Gorlin Syndrome, a familial cancer predisposing syndrome including RMS. Here, we report a newborn diagnosed with congenital embryonal RMS. Whole-exome sequencing (WES) identified the presence of two heterozygous germline mutations in two target genes of the SHH signaling pathway. The PTCH1 mutation p.(Gly38Glu) is inherited from the mother, whereas the PTCH2 p.(His622Tyr) mutation is transmitted from the father. Quantitative RT-PCR expression analysis of GLI and SMO, key players of the SHH pathway, showed significantly increase in the tumor tissue of the patient and also enrichment in the germline sample in comparison to the parents indicating activation of the SHH pathway in the patient. These findings demonstrate that SHH pathway activity seems to play a role in eRMS as evidenced by high expression levels of GLI1 RNA transcripts. We speculate that PTCH2 modulates tumorigenesis linked to the PTCH1 mutation and is likely associated with the congenital onset of the RMS observed in our patient.
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PMID:Congenital embryonal rhabdomyosarcoma caused by heterozygous concomitant PTCH1 and PTCH2 germline mutations. 2923 40