Multiple chromoanasynthesis in a rare case of sporadic renal leiomyosarcoma: case report
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE151766 | GEO | 2020/06/04
REPOSITORIES: GEO
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Project description:Down syndrome is characterized by trisomy 21 or partial duplication of chromosome 21. There have been extensive studies focusing on the identification of the Down Syndrome Critical Region (DSCR). Our case aims in providing evidence that duplication of 21q21.1-q21.2 is not included in the DSCR and that it has no clinical consequences on the phenotype. Due to missing the appropriate gestational age for serological screening, Non-Invasive Prenatal Testing (NIPT) analysis was performed for a pregnant woman with normal prenatal examinations at 22 weeks of gestation. The result of NIPT revealed a 5.8Mb maternally inherited duplication of 21q21.1-q21.2. To test whether the fetus also carried this duplication, ultrasound-guided amniocentesis was conducted and the result of chromosomal microarray analysis (CMA) with amniotic fluid showed a 6.7Mb duplication of 21q21.1-q21.2 (ranging from position 18,981,715 to 25,707,009) for the fetus. This partial duplication of 21q21.1-q21.2 for the fetus was maternally inherited. The pregnant woman and her family decided to continue the pregnancy after genetic counseling. This case clearly indicates that 21q21.1-q21.2 duplication is not included in the DSCR and most probably has no clinical consequences on the phenotype.
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Project description:Mutations in the PTEN, TP53 and RB1 pathways are obligate events in the pathogenesis of human glioblastomas, the highest grade of astrocytoma. To investigate synergy between these tumor suppressors in mice, we induced various combinations of compound deletions conditionally in astrocytes and neural precursors in the mature brain. The resulting highly penetrant astrocytomas showed a spectrum of histopathological variation reminiscent of human tumors, and ranged from grade III to grade IV (glioblastoma). Secondary somatic mutations varied depending on the combination of initiating deletions and were relevant to human disease. Receptor tyrosine kinase amplifications were frequent in tumors initiated by combined conditional deletion of Pten and Tp53, but not when Rb, Pten and Tp53 were simultaneously deleted. Multiple mutations within PI3K and Rb pathways were acquired, however, Mapk activation was not consistently detected in astrocytomas. Gene expression profiling revealed striking similarities to previously described human astrocytoma subclasses. A subset of astrocytomas initiated outside of proliferative niches in the adult brain. Gene expression of 8 human brain samples including 2 normal brainstem and 6 brainstem low-grade gliomas were profiled using HG-U133 plus 2 arrays. Gene expression of 38 mouse tumor samples, including 24 Pten;p53 double knockout and 14 Pten;p53;Rb1 triple knockout, were profiled using Affymetrix Mouse Genome 430 v2 arrays. Copy number changes of 51 double knockout tumor samples were analysed using Roswell Park Cancer Institute 6.5k BAC arrays. Copy number changes of 21 triple knockout tumor samples were analysed using Agilent mouse genome CGH mocirarray 244A.
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Project description:We report clinical and genetic findings of a 14-year-old male with T-cell acute lymphoblastic leukemia with low-hypodiploidy. The medical history included neck pain for a month, facial nerve palsy on the right side for 6 days, fever, drowsiness, and weakness for 3 days, vomiting, diarrhea for 1 day. The physical examination presented features of hypovolemia, palsy of the facial nerve on the right side, enlarged lymph nodes, hepatosplenomegaly, sore throat, and petechiae of the skin. Radiological images indicated lesions of different organs. Bone marrow biopsy confirmed precursor T-ALL. In the FISH tests, KMT2A and BCR/ABL1 rearrangements were not observed. GTG banding revealed 3 cell clones, which confirmed the hypodiploidy. Multiplex RT-qPCR was performed. STIL/TAL1 (del1p32) gene rearrangement was found in the blast cells. Additional tests were performed using the CytoScan HD microarray technique. Molecular karyotype did not reveal hypodiploidy, but identified other abnormalities such as duplication of chromosomal regions: 4q25q35.2, 6p23.3p11.1 and 8p23.3q24.21, and the loss of heterozygosity of short arm chromosome 9. In two regions of the chromosome biallelic deletions were found at 9p21.3, including the CDKN2A, CDKN2B, IFNA1, MTAP genes and at 10q23.31, containing PTEN. The child died 9 days after diagnosis. Bone marrow biopsy, GTG banding, FISH techniques, and molecular karyotyping were used to make an accurate diagnosis. This case documents a rapid progression of the disease and unfavorable results of T-cell acute lymphoblastic leukemia with hypodiploidy.
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Project description:Mutations in the PTEN, TP53 and RB1 pathways are obligate events in the pathogenesis of human glioblastomas, the highest grade of astrocytoma. To investigate synergy between these tumor suppressors in mice, we induced various combinations of compound deletions conditionally in astrocytes and neural precursors in the mature brain. The resulting highly penetrant astrocytomas showed a spectrum of histopathological variation reminiscent of human tumors, and ranged from grade III to grade IV (glioblastoma). Secondary somatic mutations varied depending on the combination of initiating deletions and were relevant to human disease. Receptor tyrosine kinase amplifications were frequent in tumors initiated by combined conditional deletion of Pten and Tp53, but not when Rb, Pten and Tp53 were simultaneously deleted. Multiple mutations within PI3K and Rb pathways were acquired, however, Mapk activation was not consistently detected in astrocytomas. Gene expression profiling revealed striking similarities to previously described human astrocytoma subclasses. A subset of astrocytomas initiated outside of proliferative niches in the adult brain.
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