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)

Rhabdomyosarcoma is the most common soft tissue sarcoma in children. Primary breast location has been reported rarely in the literature. Most rhabdomyosarcomas encountered in the breast more commonly are metastatic disease from some primary foci in another part of the body. This report addresses the case of an adolescent girl who had primary embryonal rhabdomyosarcoma of the breast with no evidence of local invasion or metastatic disease within the spectrum of Li-Fraumeni syndrome.
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PMID:Primary embryonal rhabdomyosarcoma of the breast in an adolescent female: a case report. 980 22

A child with an unusual association of cancers is described. The patient first presented with a rhabdomyosarcoma of the right scapular muscle, and was successfully treated with chemotherapy. Six years after diagnosis of the first malignancy, the child presented with two synchronous malignancies: osteosarcoma of the jaw and adrenocortical carcinoma. Genetic mutation analysis was performed and revealed a germline p53 mutation of CGT > CAT at codon 273. The family history was negative for any other cancer consistent with the Li-Fraumeni syndrome. This case highlights the need for close surveillance of patients with p53 mutation for malignancy and describes the occurrence of two malignancies synchronously.
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PMID:Rhabdomyosarcoma, osteosarcoma, and adrenocortical carcinoma in a child with a germline p53 mutation. 1539 Feb 94

Li-Fraumeni syndrome and the LF-like syndrome, rare heritable conditions that predispose to the development of malignancy, are associated with germline mutations of the tumor suppressor gene p53. The authors describe a 14-month-old boy who presented with synchronous rhabdomyosarcoma and adrenal cortical carcinoma and a novel mutation of the p53 gene. Analysis of exons 2 through 11 of the p53 gene using the polymerase chain reaction and DNA sequencing revealed a mutation of codon 273. Although codon 273 is a known hotspot region for p53 mutation, the patient's mutation, R273H, has not been associated with development of adrenal cortical carcinoma.
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PMID:Germline p53 mutation presenting as synchronous tumors. 1609 28

A contemporaneous presentation of a second breast cancer in a mother and an extremity rhabdomyosarcoma (RMS) in her daughter led to the diagnosis of the Li Fraumeni syndrome (LFS). Although the association between LFS and RMS in young patients is well recognised 1 there are no guidelines as to how this knowledge should influence the optimal management of these patients. After reviewing the literature about the natural history of the LFS 2, the incidence of second malignancy (SMN) in RMS survivors 3-6 and the management of extremity RMS 7-9, we are concerned that contemporary RMS treatment, combining non-mutilating surgery with chemoradiotherapy, may be associated with an excessive SMN risk in LFS patients with advanced RMS. We question whether treatment should be individualised and, where possible and acceptable to the family, measures such as amputation should be the considered to attain local control for LFS patients with RMS as this will avoid the need for local radiotherapy without compromising long-term function and quality of life 10.
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PMID:Recognition of Li Fraumeni syndrome at diagnosis of a locally advanced extremity rhabdomyosarcoma. 1653 90

We present a case of a 14-year-old male with a germline TP53 mutation who presented with synchronous primitive neuroectodermal tumor and choroid plexus carcinoma. Identification of synchronous brain tumors prompted genetic testing for predisposition to malignancy. Within 5 months of presentation, the child developed widely metastatic alveolar rhabdomyosarcoma. Patient DNA sequencing showed a TP53 allele with a premature stop codon in the oligomerization/nuclear export signal (NES) domain (R342ter). The child's parents, younger brother, paternal grandparents, and maternal grandmother, are without history of malignancy. The patient's brother tested negative for TP53 mutations. This case identifies a rare, de novo, germline TP53 mutation presenting with synchronous CNS malignancies and exhibiting a more fulminant course than typical cases of Li-Fraumeni syndrome.
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PMID:De novo germline TP53 mutation presenting with synchronous malignancies of the central nervous system. 1971 36

Distinguishing a lymphadenopathy from neck swelling due to other causes may not be easy in children. The authors describe a case of an 18-month-old child who presented with unilateral partoid swelling, which was subsequently diagnosed as embryonal rhabdomysarcoma. Because of a family history of breast cancer and the association between breast cancer in a family and rhabdomyosarcoma, Li-Fraumeni syndrome, a more aggressive approach to diagnosis was pursued.
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PMID:Li-Fraumeni syndrome - What does it mean for the general practitioner and general paediatrician? 2040 Dec 24

BACKGROUND Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome. Most families fulfilling the classical diagnostic criteria harbour TP53 germline mutations. However, TP53 germline mutations may also occur in less obvious phenotypes. As a result, different criteria are in use to decide which patients qualify for TP53 mutation analysis, including the LFS, Li-Fraumeni-like (LFL) and Chompret criteria. We investigated which criteria for TP53 mutation analysis resulted in the highest mutation detection rate and sensitivity in Dutch families. We describe the tumour spectrum in TP53-positive families and calculated tumour type specific relative risks. METHOD A total of 180 Dutch families referred for TP53 mutation analysis were evaluated. Tumour phenotypes were verified by pathology reports or clinical records. RESULTS A TP53 germline mutation was identified in 24 families. When the Chompret criteria were used 22/24 mutations were detected (sensitivity 92%, mutation detection rate 21%). In LFS and LFL families 18/24 mutations were found (sensitivity 75%). The two mutations detected outside the 'Chompret group' were found in a child with rhabdomyosarcoma and a young woman with breast cancer. In the mutation carriers, in addition to the classical LFS tumour types, colon and pancreatic cancer were also found significantly more often than in the general population. CONCLUSION We suggest TP53 mutation testing for all families fulfilling the Chompret criteria. In addition, TP53 mutation testing can be considered in the event of childhood sarcoma and breast cancer before 30 years. In addition to the risk for established LFS tumour types, TP53-positive individuals may also have an elevated risk for pancreatic and colon cancer.
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PMID:TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. 2052 32

Germline TP53 mutations are found in Li-Fraumeni syndrome (LFS) patients, predisposed to soft tissue sarcoma and other malignancies. The mutations and succeeding genetic events are thought to cause LFS-associated cancer, whose genetic alterations have rarely been investigated. Here, we study two LFS or Li-Fraumeni-like syndrome (LFLS) patients whose cancers showed aggressive phenotypes. Patient 1 with LFS and TP53(R273H) developed a rhabdomyosarcoma twice at the ages of 18 months and 21 years. A single-nucleotide polymorphism array-based analysis revealed two amplicons in the second tumor; one at 5q11.2 containing MAP3K1 and the other at 11q22.2 containing BIRC2/3 and YAP1. Increase of kinase signaling of MAP3K1 along with anti-apoptosis function of BIRC2/3 may have facilitated progression of this tumor. Patient 2 with LFLS and wild-typeTP53 suffered from acute myeloid leukemia. The leukemic cells had TP53(I195T) and two amplicons; one at 8q24.1 containing DEPDC6 and the other at 8q24.2 containing TRIB1, MYC, and PVT1. Quantitative PCR confirmed amplification of the genes and FISH revealed co-amplification of DEPDC6 and PVT1 in the same double minutes. Quantitative RT-PCR revealed increased expression levels of TRIB1, but no or little expression of DEPDC6, MYC, and PVT1. The results indicate that TRIB1 may be the target gene in the amplicon in the leukemia cells. Mutant TP53 can be engaged in pathways triggering gene amplification through impairment of DNA double-stranded break repair. The amplified candidate oncogenes identified in this study may have played a part in cancer development and lead to the poor outcome of LFS or LFLS-associated tumors.
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PMID:Association of germline or somatic TP53 missense mutation with oncogene amplification in tumors developed in patients with Li-Fraumeni or Li-Fraumeni-like syndrome. 2148 31

Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome, typically associated with germline mutations in the TP53 gene. Despite the high penetrance of TP53 mutations, LFS patients display striking phenotypic differences, suggesting the presence of secondary risk loci. To date, all genetic modifiers in LFS have been shown to map to either TP53 or its principal negative regulator, MDM2. Given this strong association, we set out to investigate the contribution of miR-605, a recently described microRNA (miRNA) regulator of the p53-MDM2 loop. We hypothesized that, if functional, the miR-605 gene and its variant (rs2043556) could impact the cancer risk profile of TP53 mutation carriers. Consistent with this proposition, the variant G-allele of miR-605 was associated with a 10-year acceleration in the mean age of LFS tumor onset (P = 0.04) and caused a 2.6-fold reduction in the processing levels of its host miRNA (P < 0.05). We also demonstrate that miR-605 overexpression leads to a decrease in cell proliferation, clonogenicity, and migration in two rhabdomyosarcoma cell lines carrying hotspot TP53 mutations. Together, our results implicate miR-605 as a novel modifier gene of the LFS phenotype and a promising therapeutic target in TP53 mutant cancers.
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PMID:A functional variant in miR-605 modifies the age of onset in Li-Fraumeni syndrome. 2568 25

Childhood rhabdomyosarcoma (RMS) accounts for approximately 3.5% of cancer cases among children 0 to 14 years of age. Genetic conditions associated with high risk of childhood RMS include Li-Fraumeni syndrome, pleuropulmonary blastoma, Beckwith-Wiedemann syndrome, and some RASopathies, such as neurofibromatosis type 1, Costello syndrome (CS), and Noonan syndrome (NS). Here, we report the rare case of a 4-year-old girl with clinical features of NS who developed an embryonal RMS of the chest and needed emergent treatment. Molecular genetic testing identified a de novo, large, mosaic duplication of chromosome 2 encompassing the SOS1 gene, presumably caused by a mosaic, unbalanced translocation between chromosomes 2 and 17 found on routine cytogenetic analysis. Sequence analysis of all known genes causing Noonan spectrum disorders was negative. RMS has been reported in a few patients with NS, associated in very few with germline SOS1 mutations, but none with copy number abnormalities. This is the first report to our knowledge of early-onset RMS developing in a child with features of NS and a mosaic RAS pathway gene aberration, a large SOS1 duplication. We hypothesize that the inciting event for tumor development in this case is due to the germline mosaic duplication of SOS1, which was duplicated in all cells of the tumor, and the ultimate development of the tumor was further driven by multiple chromosomal aberrations in the tumor itself, all described as somatic events in isolated RMS tumors.
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PMID:Childhood Rhabdomyosarcoma in Association With a RASopathy Clinical Phenotype and Mosaic Germline SOS1 Duplication. 2725 33


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