scholarly journals Novel Chromosomal Abnormalities Identified by Comparative Genomic Hybridization in Parathyroid Adenomas1

1998 ◽  
Vol 83 (5) ◽  
pp. 1766-1770 ◽  
Author(s):  
Nallasivam Palanisamy ◽  
Yasuo Imanishi ◽  
Pulivarthi H. Rao ◽  
Hideki Tahara ◽  
R. S. K. Chaganti ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Comparative Genomic Hybridization ◽  
Tumor Suppressor Genes ◽  
Chromosomal Abnormalities ◽  
Suppressor Gene ◽  
Comparative Genomic ◽  
Parathyroid Tumor ◽  
Genomic Hybridization ◽  
Suppressor Genes ◽  
Parathyroid Adenomas

The molecular basis of parathyroid adenomatosis includes defects in the cyclin D1/PRAD1 and MEN1 genes but is, in large part, unknown. To identify new locations of parathyroid oncogenes or tumor suppressor genes, and to further establish the importance of DNA losses described by molecular allelotyping, we performed comparative genomic hybridization (CGH) on a panel of 53 typical sporadic (nonfamilial) parathyroid adenomas. CGH is a new molecular cytogenetic technique in which the entire tumor genome is screened for chromosomal gains and/or losses. Two abnormalities, not previously described, were found recurrently: gain of chromosome 16p (6 of 53 tumors, or 11%) and gain of chromosome 19p (5 of 53, or 9%). Losses were found frequently on 11p (14 of 53, or 26%), as well as 11q (18 of 53, or 34%). Recurrent losses were also seen on chromosomes 1p, 1q, 6q, 9p, 9q, 13q, and 15q, with frequencies ranging from 8–19%. Twenty-four of the 53 adenomas were also extensively analyzed with polymorphic microsatellite markers for allelic losses, either in this study (11 cases) or previously (13 cases). Molecular allelotyping results were highly concordant with CGH results in these tumors (concordance level of 97.5% for all informative markers/chromosome arms examined). In conclusion, CGH has identified the first two known chromosomal gain defects in parathyroid adenomas, suggesting the existence of direct-acting parathyroid oncogenes on chromosomes 16 and 19. CGH has confirmed the locations of putative parathyroid tumor suppressor genes, also defined by molecular allelotyping, on chromosomes 1p, 6q, 9p, 11q, 13q, and 15q. Finally, CGH has provided new evidence favoring the possibility that distinct parathyroid tumor suppressors exist on 1p and 1q, and has raised the possibility of a parathyroid tumor suppressor gene on 11p, distinct from the MEN1 gene on 11q. CGH can identify recurrent genetic abnormalities in hyperparathyroidism, especially chromosomal gains, that other methods do not detect.

Cooperation of Gene Mutations Including Class I, Class II and Tumor Suppressor Genes In Childhood Acute Myeloid Leukemia and Their Impacts on Survivals

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2713-2713
Author(s):  
Der-Cherng Liang ◽  
Lee-Yung Shih ◽  
Chao-Ping Yang ◽  
Iou-Jih Hung ◽  
Tang-Her Jaing ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Gene Mutation ◽  
Tumor Suppressor Genes ◽  
Chromosomal Abnormalities ◽  
Gene Mutations ◽  
Class Ii ◽  
Suppressor Gene ◽  
Class I ◽  
Suppressor Genes ◽  
Pediatric Aml

Abstract Abstract 2713 Background. The cooperation of gene mutations, especially their impacts on survivals of childhood acute myeloid leukemia (AML) has not been well known. Aims. Our aims were (1) to study the frequency of each gene mutation in childhood AML, (2) to study the impact of each gene mutation on the treatment outcome, and (3) to examine the cooperativity of gene mutations. Materials and Methods. From Feb. 1996 to Jan. 2010, bone marrow samples at diagnosis from 198 children with AML at Chang Gung Children's Hospital, Taoyuan and Mackay Memorial Hospital, Taipei, were analyzed for gene mutations including FLT3-ITD, FLT3-TKD (D835), c-KIT, cFMS, JAK 2V617F, NRAS, KRAS, PTPN11 (Class I mutations), RUNX1, CEBPα, NPM1 (Class II mutations), WT1 and P53 (tumor suppressor genes). The subtypes included: t(8;21) 19.9%, inv(16) 8.9%, t(15;17) 8.4%, t(9;11) 5.2%, t(10;11) 2.6%, trisomy 21 4.2%, intermediate-risk group 40.3% (including 13 patients with other MLL translocations), and poor-risk group 11.0% (including 7 patients with complex chromosomal abnormalities and 4 patients with MLL-PTD). Results. FLT3-ITD occurred in 15.0% of patients, FLT3-TKD 7.2%, c-KIT 11.5%, c-FMS 2.9%, JAK2V617F 3.3%, NRAS 9.1%, KRAS 7.7%, PTPN11 3.3%, RUNX1 2.7%, CEBPα 7.9%, NPM1 4.1%, WT1 3.9% and P53 1.7%. Taken together, 52.5% of patients had Class I gene mutations, 13.1% had Class II gene mutations, and 5.1% had WT1 or P53 mutations. In all, 59.1% of patients had Class I, Class II or tumor suppressor gene mutations. Only one patient (0.5 %) had gene mutations involving all Class I, Class II and tumor suppressor genes. Ninety-eight patients, who were treated with Taiwan Pediatric Oncology Group (TPOG) APL protocols (for acute promyelocytic leukemia) and TPOG 97A protocol (for other AML) (Liang et al, Leukemia 2006), were analyzed for survivals. In patients with t(8;21), the 5-year event-free survival (EFS) was 66±12%; 71±17% for patients with c-KIT mutations and 50±35% for the 2 patients with JAK2V617F. In patients with inv(16), the EFS of 70±15% seemed to be compromised (60±22%) for those with c-KIT mutations. In patients with t(15;17), the EFS of 78±11% was not compromised by FLT3-ITD or FLT3-TKD mutations. In patients with t(9;11), the EFS of 64% seemed to be compromised (50±35%) in the 2 patients with FLT3-TKD mutations. In 3 patients with t(10;11), no gene mutations were found. In trisomy 21, the EFS of 75±22% seemed to be compromised (50±35%) in the 2 patients with CEBPα mutations. Of the 5 patients with complex chromosomal abnormalities, the only one patient carrying RUNX1 survived. Of the 3 patients with MLL-PTD having an EFS of 33±27%, one each patient with c-FMS or WT1 mutation died. The only one patient who had all Class I, Class II and tumor suppressor gene mutations (FLT3-TKD+ CEBPα+ WT1) died in induction therapy. Two of the other 4 patients who had 3 mutations acrossing 2 classes had EFS of 6 and 10 months, respectively. Conclusions. Our study on a large cohort of pediatric AML patients revealed that 59.1% patients had at least one gene mutation. That 3 of 5 patients who had 3 gene mutations soon failed suggested that gene mutations, especially in 3 combinations, might compromise the survival. Further study on more patients is warranted to explore more of the prognostic significance of cooperating gene mutations in pediatric AML. (Supported by grants MMH-E-98009, NSC 96–2314-B-195-006-MY3, NHRI-EX-96-9434SI and DOH99-TD-C-111-006.) Disclosures: No relevant conflicts of interest to declare.

Comparative Genomic Hybridization to Dna Microarrays

1997 ◽  
Vol 3 (S2) ◽  
pp. 205-206
Author(s):  
D. Pinkel ◽  
R. Segraves ◽  
D. Sudar ◽  
L. van Vliet ◽  
S. Clark ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Copy Number ◽  
Dna Microarrays ◽  
Suppressor Gene ◽  
Comparative Genomic ◽  
Cancer Genes ◽  
Genomic Hybridization ◽  
Metaphase Chromosomes ◽  
Number Variation ◽  
Genetic Events

Comparative genomic hybridization (CGH), which involves the simultaneous hybridization of differentially labeled total genomic DNA from test cells and reference normal cells to metaphase chromosomes, has been used extensively to screen tumor genomes for regions of DNA sequence copy number variation. Analysis of these hybridizations requires quantitative analysis of the ratio of intensities of the fluorescent hybridization signals as a function of position along the chromosomes, which basically serve as a convenient genetic map. The ratios need to be measured very accurately since changes of about ± 20% from the average for the genome indicate important genetic events. Widespread use of CGH over the past several years has identified numerous regions of the genome that may contain currently unknown cancer genes. For example, regions of increased copy number may indicate sites of oncogenes, while regions of copy number decrease relative to average for the genome may signify the presence of a tumor suppressor gene.

scholarly journals Chromosomal imbalances identified by comparative genomic hybridization in sporadic parathyroid adenomas

2002 ◽  
pp. 209-213 ◽  
Author(s):  
JL Garcia ◽  
JC Tardio ◽  
NC Gutierrez ◽  
MB Gonzalez ◽  
JM Hernandez ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Genetic Gain ◽  
Chromosome 9 ◽  
Comparative Genomic ◽  
Chromosome 11 ◽  
Genomic Hybridization ◽  
Genomic Amplification ◽  
Chromosomal Imbalances ◽  
Parathyroid Adenomas ◽  
Gains And Losses

OBJECTIVE: To identify chromosomal gains and losses in sporadic parathyroid adenomas (PAs). METHODS: Fourteen sporadic PAs were studied by comparative genomic hybridization (CGH). RESULTS: The fourteen studied PAs showed chromosomal imbalances. All cases except one exhibited two or more abnormalities. Chromosomal gains were found in all cases, and three cases (21%) also presented chromosomal losses. Genomic amplification was not observed. Chromosome 9 was involved in ten cases. Recurrent genetic gain was found on 9p22-24 and on 9q34, each in 6 of 14 cases (43%). Other recurrent gains included Xq26 in 6 PAs (43%) and 4q21-28 and 8p22-23, each in 4 of 14 cases (29%). Regions of recurrent genetic loss involved whole chromosome 11 and 20q12-13, each in 2 of 14 cases (14%). CONCLUSIONS: Our findings show chromosomal imbalances in all sporadic PAs studied by CGH, partly confirming previous reports, with the exception that we observed more chromosomal gains than losses. Several regions (9p22-24, 9q34, Xq26, 4q21-28, and 8p22-23) probably deserve further investigation in order to discard the presence of genes involved in parathyroid tumorigenesis.

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