scholarly journals Typical numerical alterations in genome identified by array CGH analysis in neuroblastoma tumors

2021 ◽  
Vol 8 (4) ◽  
pp. 248-256
Author(s):  
Katarzyna Szewczyk ◽  
◽  
Keyword(s):  
Array Cgh ◽  
Positive Impact ◽  
Good Prognosis ◽  
Chromosome 17 ◽  
Mycn Amplification ◽  
Chromosome 14 ◽  
Genetic Changes ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Tumor Genome

<abstract><sec> <title>Introduction</title> <p>The clinical variability in the course of neuroblastoma (NB) is closely linked to diverse genetic changes acquired by tumor cells. Rapid NB progression is associated with oncogene MYCN amplification (MNA) and segmental chromosomal aberrations (SCA). Alternatively, numerical chromosomal alterations (NCA) have positive impact on treatment. So far, no studies have been undertaken to identify NCA that may group NB patients. Therefore, the aim of the study was to identify NCA typical for NB.</p> </sec><sec> <title>Materials and methods</title> <p>Copy number alterations in NB tumor genome (fresh samples N = 94; formalin-fixed paraffin-embedded specimens N = 66) were analyzed with a pangenomic array CGH technique.</p> </sec><sec> <title>Results</title> <p>The profile with NCA was observed in 72 (45%) cases, NCA+SCA in 37 (23%), normal in 35 (22%) and MNA in 16 (10%). Samples with NCA were characterized by whole chromosome gains: 17, 7, 6 (78%, 65%, 51%, respectively) and copy loss of chromosome 14 (57%). Similarly to NCA, patients with a combined NCA and SCA profile were also characterized by gain of whole chromosome 17 and 7 (35% both) and loss of chromosome 14 (38%), but with lower frequency. In the combined NCA and SCA profiles, typical NB changes such as deletion 1p36 (27%) and gain 17q (41%) were observed, as well as deletion 11q (24%). The same alterations were detected in MNA samples (44%, 44%, 19%, respectively). A difference was found in spanning 11q deletion between MNA and NCA+SCA subgroup, which may suggest new prognostic markers in NB. In MNA subgroup specific NCA was not indicated.</p> </sec><sec> <title>Conclusions</title> <p>The hypothesis that NCA in NB tumors are more frequent in younger children with good prognosis was confirmed. To gain new insights into the pathogenesis of NB and to establish molecular targets for diagnosis and therapy, candidate genes in the altered chromosomal regions must be investigated.</p> </sec></abstract>

Comprehensive Genetic and Histopathologic Study Reveals Three Types of Neuroblastoma Tumors

2001 ◽  
Vol 19 (12) ◽  
pp. 3080-3090 ◽  
Author(s):  
Maria Łastowska ◽  
Catherine Cullinane ◽  
Sadick Variend ◽  
Simon Cotterill ◽  
Nick Bown ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Genetic Alterations ◽  
Good Prognosis ◽  
Mycn Amplification ◽  
Genetic Changes ◽  
Pathology Classification ◽  
Genetic Features ◽  
1P Deletion ◽  
Tumor Types ◽  
Type 3

PURPOSE: To determine the relationship between multiple genetic features, tumor morphology, and prognosis in neuroblastoma. PATIENTS AND METHODS: The genetic alterations and morphologic features that underpin three histopathologic risk classifications were analyzed in 108 neuroblastoma patients. Tumors were subdivided into four groups based on the three most frequent and prognostically significant genetic alterations (17q gain, 1p deletion, and MYCN amplification), and all other genetic, morphologic, and clinical data were analyzed with respect to these groups. RESULTS: Our analyses identify three nonoverlapping tumor types with distinct genetic and morphologic features, defined here as types 1, 2, and 3. Type 1 tumors show none of the three significant genetic alterations and have good prognosis. Both type 2 (17q gain only or 17q gain and 1p del) and type 3 (17q gain, 1p del, and MYCN amplification) tumors progress. However, these tumor types are distinguished clinically by having significantly different median age at diagnosis and median progression-free survival (PFS). Multivariate analysis indicates that 17q gain is the only independent prognostic factor among all genetic, histopathologic, and clinical factors analyzed. Among histopathologic risk systems, the International Neuroblastoma Pathology Classification was the best predictor of PFS. CONCLUSION: Our results indicate that specific combinations of genetic changes in neuroblastoma tumors contribute to distinct morphologic and clinical features. Furthermore, the identification of two genetically and morphologically distinct types of progressing tumors suggests that possibilities for different therapeutic regimens should be investigated.

scholarly journals Application of array CGH on archival formalin-fixed paraffin-embedded tissues including small numbers of microdissected cells

2006 ◽  
Vol 86 (9) ◽  
pp. 968-978 ◽  
Author(s):  
Nicola A Johnson ◽  
Rifat A Hamoudi ◽  
Koichi Ichimura ◽  
Lu Liu ◽  
Danita M Pearson ◽  
...  
Keyword(s):  
Array Cgh ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Formalin-fixed paraffin-embedded clinical tissues show spurious copy number changes in array-CGH profiles

2007 ◽  
Vol 72 (5) ◽  
pp. 441-447 ◽  
Author(s):  
EA Mc Sherry ◽  
A Mc Goldrick ◽  
EW Kay ◽  
AM Hopkins ◽  
WM Gallagher ◽  
...  
Keyword(s):  
Copy Number ◽  
Array Cgh ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Copy Number Changes ◽  
Formalin Fixed

scholarly journals Droplet Digital PCR Measurement of HER2 Copy Number Alteration in Formalin-Fixed Paraffin-Embedded Breast Carcinoma Tissue

2013 ◽  
Vol 59 (6) ◽  
pp. 991-994 ◽  
Author(s):  
Phillip Belgrader ◽  
Stephanie C Tanner ◽  
John F Regan ◽  
Ryan Koehler ◽  
Benjamin J Hindson ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Copy Number ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Invasive Breast Carcinoma ◽  
Chromosome 17 ◽  
Analysis Tool ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

BACKGROUND Human epidermal growth factor receptor 2 (HER2) testing is routinely performed by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) analyses for all new cases of invasive breast carcinoma. IHC is easier to perform, but analysis can be subjective and variable. FISH offers better diagnostic accuracy and added confidence, particularly when it is used to supplement weak IHC signals, but it is more labor intensive and costly than IHC. We examined the performance of droplet digital PCR (ddPCR) as a more precise and less subjective alternative for quantifying HER2 DNA amplification. METHODS Thirty-nine cases of invasive breast carcinoma containing ≥30% tumor were classified as positive or negative for HER2 by IHC, FISH, or both. DNA templates for these cases were prepared from formalin-fixed paraffin-embedded (FFPE) tissues to determine the HER2 copy number by ddPCR. ddPCR involved emulsifying hydrolysis probe–based PCR reaction mixtures containing the ERBB2 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian); also known as HER2] gene and chromosome 17 centromere assays into nanoliter-sized droplets for thermal cycling and analysis. RESULTS ddPCR distinguished, through differences in the level of HER2 amplification, the 10 HER2-positive samples from the 29 HER2-negative samples with 100% concordance to HER2 status obtained by FISH and IHC analysis. ddPCR results agreed with the FISH results for the 6 cases that were equivocal by IHC analyses, confirming 2 of these samples as positive for HER2 and the other 4 as negative. CONCLUSIONS ddPCR can be used as a molecular-analysis tool to precisely measure copy number alterations in FFPE samples of heterogeneous breast tumor tissue.

O8: Array CGH Using Whole Genome Amplification Of Fresh Frozen And Formalin-Fixed, Paraffin-Embedded Tumour DNA

2005 ◽  
Vol 48 (4) ◽  
pp. 457-458
Author(s):  
Suzanne Little ◽  
Raisa Vuononvirta ◽  
Jorge Reis-Filho ◽  
Marjan Iravani ◽  
Kerry Fenwick ◽  
...  
Keyword(s):  
Whole Genome Amplification ◽  
Array Cgh ◽  
Whole Genome ◽  
Genome Amplification ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Fresh Frozen ◽  
Formalin Fixed

scholarly journals Array CGH using whole genome amplification of fresh-frozen and formalin-fixed, paraffin-embedded tumor DNA

Genomics ◽  
2006 ◽  
Vol 87 (2) ◽  
pp. 298-306 ◽  
Author(s):  
Suzanne E. Little ◽  
Raisa Vuononvirta ◽  
Jorge S. Reis-Filho ◽  
Rachael Natrajan ◽  
Marjan Iravani ◽  
...  
Keyword(s):  
Whole Genome Amplification ◽  
Array Cgh ◽  
Whole Genome ◽  
Genome Amplification ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Fresh Frozen ◽  
Tumor Dna ◽  
Formalin Fixed

scholarly journals 3′RNA Sequencing Accurately Classifies Formalin-Fixed Paraffin-Embedded Uterine Leiomyomas

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3839
Author(s):  
Miika Mehine ◽  
Sara Khamaiseh ◽  
Terhi Ahvenainen ◽  
Tuomas Heikkinen ◽  
Anna Äyräväinen ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Cost Effective ◽  
Uterine Leiomyomas ◽  
Reproductive Age ◽  
Genetic Changes ◽  
Formalin Fixed Paraffin ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded ◽  
Fresh Frozen ◽  
Formalin Fixed

Uterine leiomyomas are benign smooth muscle tumors occurring in 70% of women of reproductive age. The majority of leiomyomas harbor one of three well-established genetic changes: a hotspot mutation in MED12, overexpression of HMGA2, or biallelic loss of FH. The majority of studies have classified leiomyomas by complex and costly methods, such as whole-genome sequencing, or by combining multiple traditional methods, such as immunohistochemistry and Sanger sequencing. The type of specimens and the amount of resources available often determine the choice. A more universal, cost-effective, and scalable method for classifying leiomyomas is needed. The aim of this study was to evaluate whether RNA sequencing can accurately classify formalin-fixed paraffin-embedded (FFPE) leiomyomas. We performed 3′RNA sequencing with 44 leiomyoma and 5 myometrium FFPE samples, revealing that the samples clustered according to the mutation status of MED12, HMGA2, and FH. Furthermore, we confirmed each subtype in a publicly available fresh frozen dataset. These results indicate that a targeted 3′RNA sequencing panel could serve as a cost-effective and robust tool for stratifying both fresh frozen and FFPE leiomyomas. This study also highlights 3′RNA sequencing as a promising method for studying the abundance of unexploited tissue material that is routinely stored in hospital archives.

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