ALK Gene Copy Number Gain and Immunohistochemical Expression Status Using Three Antibodies in Neuroblastoma

2017 ◽  
Vol 20 (2) ◽  
pp. 133-141 ◽  
Author(s):  
Eun Kyung Kim ◽  
Sewha Kim
Keyword(s):  
Copy Number ◽  
Gene Copy Number ◽  
Stage Iv ◽  
Copy Number Gain ◽  
High Risk Group ◽  
Gene Copy ◽  
Clinicopathological Parameters ◽  
Mycn Amplification ◽  
Anaplastic Lymphoma ◽  
Poorly Differentiated

Anaplastic lymphoma kinase ( ALK) gene aberrations—such as mutations, amplifications, and copy number gains—represent a major genetic predisposition to neuroblastoma (NB). This study aimed to evaluate the correlation between ALK gene copy number status, ALK protein expression, and clinicopathological parameters. We retrospectively retrieved 30 cases of poorly differentiated NB and constructed tissue microarrays (TMAs). ALK copy number changes were assessed by fluorescence in situ hybridization (FISH) assays, and ALK immunohistochemistry (IHC) testing was performed using three different antibodies (ALK1, D5F3, and 5A4 clones). ALK amplification and copy number gain were observed in 10% (3/30) and 53.3% (16/30) of the cohort, respectively. There were positive correlations between ALK copy number and IHC-positive rate in ALK1 and 5A4 antibodies ( P < 0.001 and P = 0.019, respectively). ALK1, D5F3, and 5A4 antibodies equally showed 100% sensitivity in detecting ALK amplification. However, the sensitivity for detecting copy number gain differed among the three antibodies, with 75% sensitivity in D5F3 and 0% sensitivity in ALK1. ALK-amplified NBs were correlated with synchronous MYCN amplification and chromosome 1p deletion. ALK IHC positivity was frequently observed in INSS stage IV and high-risk group patients. In conclusion, this study identified that an increase in the ALK copy number is a frequent genetic alteration in poorly differentiated NB. ALK-amplified NBs showed consistent ALK IHC positivity with all kinds of antibodies. In contrast, the detection performance of ALK copy number gain was antibody dependent, with the D5F3 antibody showing the best sensitivity.

scholarly journals Top-level MET gene copy number gain defines a subtype of poorly differentiated pulmonary adenocarcinomas with poor prognosis

2020 ◽  
Vol 9 (3) ◽  
pp. 603-616 ◽  
Author(s):  
Tobias Raphael Overbeck ◽  
Dana Alina Cron ◽  
Katja Schmitz ◽  
Achim Rittmeyer ◽  
Wolfgang Körber ◽  
...  
Keyword(s):  
Copy Number ◽  
Poor Prognosis ◽  
Gene Copy Number ◽  
Copy Number Gain ◽  
Gene Copy ◽  
Poorly Differentiated ◽  
Gene Copy Number Gain

Clinicopathologic Implications of ALK Gene Copy Number Gain in Non-small Cell Lung Cancer

2011 ◽  
Vol 10 (2) ◽  
pp. 87 ◽  
Author(s):  
Seol-Bong Yoo ◽  
Hyojin Kim ◽  
Xianhua Xu ◽  
Ping-Li Sun ◽  
Yan Jin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Copy Number Gain ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung ◽  
Gene Copy Number Gain

scholarly journals Copy number gain of CMTM6 increases the expression of PD-L1 in undifferentiated pleomorphic sarcoma

2021 ◽  
Author(s):  
Shin Ishihara ◽  
Takeshi Iwasaki ◽  
Kenichi Kohashi ◽  
Yuichi Yamada ◽  
Yu Toda ◽  
...  
Keyword(s):  
Copy Number ◽  
Transmembrane Domain ◽  
Gene Copy Number ◽  
Copy Number Gain ◽  
The Cancer Genome Atlas ◽  
Gene Copy ◽  
Undifferentiated Pleomorphic Sarcoma ◽  
Pleomorphic Sarcoma ◽  
Number Variation ◽  
Cancer Genome Atlas

Abstract Background Undifferentiated pleomorphic sarcoma (UPS) is a sarcoma with a poor prognosis. A clinical trial, SARC028, revealed that treatment with anti-PD-1 drugs was effective against UPS. Studies have reported that UPS expresses PD-L1, sometime strongly (≥ 50%). However, the mechanism of PD-L1 expression in UPS has remained still unclear. CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) was identified as a novel regulator of PD-L1 expression. The positive relationship between PD-L1 and CMTM6 has been reported in several studies. The aim of this study was to examine CMTM6 expression in UPS and evaluate the relationship between PD-L1 and CMTM6. Materials and methods Fifty-one primary UPS samples were subjected to CMTM6 and PD-L1 immunostaining. CMTM6 expression was assessed using proportion and intensity scores. CMTM6 gene copy number was also evaluated using a real-time PCR-based copy number assay. We also analyzed the mRNA expression and copy number variation of PD-L1 and CMTM6 in The Cancer Genome Atlas (TCGA) data. Results TCGA data indicated that the mRNAs encoded by genes located around 3p22 were coexpressed with CMTM6 mRNA in UPS. Both proportion and intensity scores of CMTM6 positively correlated with strong PD-L1 expression (≥ 50%) (both p = 0.023). CMTM6 copy number gain increased CMTM6 expression. Patients with UPS with a high CMTM6 intensity score had worse prognosis for overall survival. Conclusions CMTM6 expression was significantly correlated with PD-L1 expression. CMTM6 expression induced strong PD-L1 expression (≥ 50%). CMTM6 copy number gain promoted CMTM6 expression and increased PD-L1 expression in UPS.

MYC and human telomerase gene (TERC) gene copy number gain in resected in non-small cell lung cancer (NSCLC).

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 10580-10580 ◽  
Author(s):  
A. Flacco ◽  
V. Ludovini ◽  
F. R. Tofanetti ◽  
F. Bianconi ◽  
G. Bellezza ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Copy Number Gain ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung ◽  
Human Telomerase ◽  
Gene Copy Number Gain

scholarly journals Association of copy number variation in the AHI1 gene with risk of obesity in the Chinese population

2012 ◽  
Vol 166 (4) ◽  
pp. 727-734 ◽  
Author(s):  
Liansha Huang ◽  
Dacai Teng ◽  
Hao Wang ◽  
Guoqing Sheng ◽  
Tonghua Liu
Keyword(s):  
Copy Number ◽  
Integration Site ◽  
Linear Trend ◽  
Copy Number Variants ◽  
Gene Copy Number ◽  
Copy Number Gain ◽  
Gene Copy ◽  
Significant Linear Trend ◽  
Number Variation ◽  
Dna Copy Number Change

ObjectiveThe prevalence of obesity has increased dramatically over the past decade. Gene copy number variants (CNVs) have been recognized as a hereditable source of susceptibility in human complex diseases including obesity. Recent studies have shown that Abelson helper integration site 1 (Ahi1) gene has a significant contribution in the homeostasis regulation in mouse models of obesity. A study was therefore carried out to investigate whether CNVs inAHI1gene contribute to human obesity.Subjects and methodsWe analyzed samples from 70 Chinese overweight adults and 74 healthy controls for DNA copy number change using the Affymetrix single-nucleotide polymorphism (SNP) 6.0 array. Validation of CNVs ofAHI1was achieved by real-time PCR using the ΔΔCtmethod.ResultsCopy number gain analysis revealed significant gains (P=0.0017) ofAHI1gene copy number in 17 of 70 (24.3%) samples but only four of 74 (5.4%) controls overall. Then we studied the frequency distribution of CNVs inAHI1gene according to body mass index (BMI) grade. Five out of 28 (18.5%) at-risk obese, six out of 26 (26.9%) moderate obese, and six out of 17 (29.4%) severe obese subjects studied showed increasedAHI1gene copy number.ConclusionsThe result suggested that there was a significant linear trend for increasingAHI1gene copy number frequencies with increasing BMI.

Sign in / Sign up

Export Citation Format

Share Document