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

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

Research output: Contribution to journalArticle

37 Citations (Scopus)

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. 63 years, 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.

Original languageEnglish (US)
Pages (from-to)470-474
Number of pages5
JournalGynecologic Oncology
Volume128
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

Fingerprint

Microsatellite Instability
Mutation
Genes
Neoplasms
Exome
Atlases
Endometrial Neoplasms
Disease-Free Survival
Exons
Genome
Mutation Rate
Fluorescence Microscopy
Nucleotides
Complementary DNA
Genotype
Students
Recurrence
Cell Line

Keywords

  • Endometrial cancer
  • Microsatellite instability
  • RPL22

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Novetsky, A. P., Zighelboim, I., Thompson, D. M., Powell, M. A., Mutch, D. G., & Goodfellow, P. J. (2013). Frequent mutations in the RPL22 gene and its clinical and functional implications. Gynecologic Oncology, 128(3), 470-474. https://doi.org/10.1016/j.ygyno.2012.10.026

Frequent mutations in the RPL22 gene and its clinical and functional implications. / Novetsky, Akiva P.; Zighelboim, Israel; Thompson, Dominic M.; Powell, Matthew A.; Mutch, David G.; Goodfellow, Paul J.

In: Gynecologic Oncology, Vol. 128, No. 3, 03.2013, p. 470-474.

Research output: Contribution to journalArticle

Novetsky, AP, Zighelboim, I, Thompson, DM, Powell, MA, Mutch, DG & Goodfellow, PJ 2013, 'Frequent mutations in the RPL22 gene and its clinical and functional implications', Gynecologic Oncology, vol. 128, no. 3, pp. 470-474. https://doi.org/10.1016/j.ygyno.2012.10.026
Novetsky AP, Zighelboim I, Thompson DM, Powell MA, Mutch DG, Goodfellow PJ. Frequent mutations in the RPL22 gene and its clinical and functional implications. Gynecologic Oncology. 2013 Mar;128(3):470-474. https://doi.org/10.1016/j.ygyno.2012.10.026
Novetsky, Akiva P. ; Zighelboim, Israel ; Thompson, Dominic M. ; Powell, Matthew A. ; Mutch, David G. ; Goodfellow, Paul J. / Frequent mutations in the RPL22 gene and its clinical and functional implications. In: Gynecologic Oncology. 2013 ; Vol. 128, No. 3. pp. 470-474.
@article{7339637900df4fb6b73eb3161645789c,
title = "Frequent mutations in the RPL22 gene and its clinical and functional implications",
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. 63 years, 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.",
keywords = "Endometrial cancer, Microsatellite instability, RPL22",
author = "Novetsky, {Akiva P.} and Israel Zighelboim and Thompson, {Dominic M.} and Powell, {Matthew A.} and Mutch, {David G.} and Goodfellow, {Paul J.}",
year = "2013",
month = "3",
doi = "10.1016/j.ygyno.2012.10.026",
language = "English (US)",
volume = "128",
pages = "470--474",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Frequent mutations in the RPL22 gene and its clinical and functional implications

AU - Novetsky, Akiva P.

AU - Zighelboim, Israel

AU - Thompson, Dominic M.

AU - Powell, Matthew A.

AU - Mutch, David G.

AU - Goodfellow, Paul J.

PY - 2013/3

Y1 - 2013/3

N2 - 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. 63 years, 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.

AB - 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. 63 years, 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.

KW - Endometrial cancer

KW - Microsatellite instability

KW - RPL22

UR - http://www.scopus.com/inward/record.url?scp=84873741277&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873741277&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2012.10.026

DO - 10.1016/j.ygyno.2012.10.026

M3 - Article

VL - 128

SP - 470

EP - 474

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 3

ER -