Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Mar;128(3):470-4.
doi: 10.1016/j.ygyno.2012.10.026. Epub 2012 Nov 2.

Frequent mutations in the RPL22 gene and its clinical and functional implications

Akiva P Novetsky  1 , Israel Zighelboim, Dominic M Thompson Jr, Matthew A Powell, David G Mutch, Paul J Goodfellow
Affiliations

Frequent mutations in the RPL22 gene and its clinical and functional implications

Akiva P Novetsky et al. Gynecol Oncol. 2013 Mar.

Abstract

Objective: To determine the frequency and spectrum of mutations in RPL22 a gene identified by The Cancer Genome Atlas (TCGA) as mutated in endometrioid endometrial cancer, and determine the relationship between RPL22 defects and clinicopathologic features.

Methods: Direct sequencing of the entire coding region of the RPL22 cDNA and exons 2/4 was performed in tumors with/without microsatellite instability (MSI). RPL22 expression was assessed by immunofluorescence microscopy in the KLE, RL952 and AN3CA cell lines, wildtype, heterozygous and homozygous mutants, respectively. Relationships between RPL22 mutation and clinicopathological features were assessed using Chi-squared analysis and Student's t test. Progression-free survival (PFS) was calculated from the date of diagnosis to the date of recurrence.

Results: A single nucleotide deletion in an A8 coding repeat was identified in exon 2 of the RPL22 gene in 116/226 (52%) of MSI-high tumors. No mutations were identified in MSI-stable tumors. Only 2% of the tumors expressed a homozygous A deletion. RPL22 mutation was not associated with stage, grade, race and lymphovascular space invasion. Women whose tumors harbored RPL22 mutations were significantly older (67 vs. 63years, p=0.005). There was no difference in PFS between patients with the wildtype and mutant genotypes.

Conclusions: RPL22 is frequently mutated in MSI-high endometrioid endometrial cancers. The A8 mutation identified was not reported in the whole exome sequences analyzed by the TCGA. The demonstration of frequent mutation in RPL22 may point to a limitation of the exome capture and next generation sequencing analysis methods for some mononucleotide string mutations. Functional assessment of the RPL22 knockdown may be warranted.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
RPL22 mutation analysis and expression. A. Chromatograms demonstrating the wildtype RPL22 sequence, heterozygous and homozygous deletions of a single nucleotide. B. Immunofluorescence demonstrating RPL22 expression in the KLE (wildtype) and RL952 (heterozygous deletion) cell lines and absence of expression in the AN3CA (homozygous deletion) cell line.
Figure 2
Figure 2
Kaplan-Meier survival curves demonstrating no difference in progression-free survival between patients with wildtype and mutant RPL22.
See this image and copyright information in PMC

References

    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012 Jan;62(1):10–29. - PubMed
    1. Howlader N, Noone A, Krapcho M, Neyman N, Aminou R, Altekruse S, et al. SEER Cancer Statistics Review, 1975–2009 (Vintage 2009 Populations) [Internet] Available from: http://seer.cancer.goc/vsr/1975_2009_pops09.
    1. Lewin SN, Herzog TJ, Barrena Medel NI, Deutsch I, Burke WM, Sun X, et al. Comparative performance of the 2009 international Federation of gynecology and obstetrics' staging system for uterine corpus cancer. Obstetrics & …. 2010 Nov;116(5):1141–1149. - PubMed
    1. The Cancer Genome Atlas (TCGA) Pilot Project [Internet] cancergenome.nih.gov. [cited 2012 Jun. 13]. Available from: http://cancergenome.nih.gov/PublishedContent/Files/pdfs/6.5.2.1_TCGA_Pil....
    1. Anderson SJ, Lauritsen JPH, Hartman MG, Foushee AMD, Lefebvre JM, Shinton SA, et al. Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint. Immunity. 2007 Jun;26(6):759–772. - PubMed

LinkOut - more resources