Increased transversions in a novel mutator colon cancer cell line

Increased transversions in a novel mutator colon cancer cell line

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ABSTRACT We describe a novel mutator phenotype in the Vaco411 colon cancer cell line which increases the spontaneous mutation rate 10–100-fold over background. This mutator results primarily in transversion base substitutions which are found infrequently in repair competent cells. Of the four possible types of transversions, only three were principally recovered. Spontaneous mutations recovered also included transitions and large deletions, but very few frameshifts were recovered. When compared to known mismatch repair defective colon cancer mutators, the distribution of mutations in Vaco411 is significantly different. Consistent with this difference, Vaco411 extracts are proficient in assays of mismatch repair. The Vaco411 mutator appears to be novel, and is not an obvious human homologue of any of the previously characterized bacterial or yeast transversion phenotypes. Several hypotheses by which this mutator may produce transversions are presented. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS INHERITED _MUTYH_ MUTATIONS CAUSE ELEVATED SOMATIC MUTATION RATES AND DISTINCTIVE MUTATIONAL SIGNATURES IN NORMAL HUMAN CELLS Article Open access 08 July 2022 RATE VOLATILITY AND ASYMMETRIC SEGREGATION DIVERSIFY MUTATION BURDEN IN CELLS WITH MUTATOR ALLELES Article Open access 04 January 2021 PERVASIVE LESION SEGREGATION SHAPES CANCER GENOME EVOLUTION Article 24 June 2020 AUTHOR INFORMATION Author notes * James R Eshleman Present address: Department of Pathology, Ross 632, AUTHORS AND AFFILIATIONS * Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, Suite 200, UCRC II, 11001 Cedar Road, Cleveland, 44106, Ohio, USA James R Eshleman * Department of Medicine, University Hospitals of Cleveland and Case Western Reserve University, Suite 200, UCRC II, 11001 Cedar Road, Cleveland, 44106, Ohio, USA P Scott Donover, Sandra E Swinler, James D Lutterbaugh, James KV Willson, W David Sedwick & Sanford D Markowitz * Department of General Medical Sciences and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Suite 200, UCRC II, 11001 Cedar Road, Cleveland, 44106, Ohio, USA Martina L Veigl * Department of Biochemistry and Howard Hughes Medical Institute, Nanaline Duke Building, Durham, 27710, North Carolina, USA Guo-Min Li & Paul Modrich * Department of Medicine-Oncology, Duke University Medical Center, Nanaline Duke Building, Durham, 27710, North Carolina, USA Susan J Littman * Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, 21205, Maryland, USA James R Eshleman * Department of Pathology, University of Kentucky Medical Center, Lexington, 40536, Kentucky, USA Guo-Min Li Authors * James R Eshleman View author publications You can also search for this author inPubMed Google Scholar * P Scott Donover View author publications You can also search for this author inPubMed Google Scholar * Susan J Littman View author publications You can also search for this author inPubMed Google Scholar * Sandra E Swinler View author publications You can also search for this author inPubMed Google Scholar * Guo-Min Li View author publications You can also search for this author inPubMed Google Scholar * James D Lutterbaugh View author publications You can also search for this author inPubMed Google Scholar * James KV Willson View author publications You can also search for this author inPubMed Google Scholar * Paul Modrich View author publications You can also search for this author inPubMed Google Scholar * W David Sedwick View author publications You can also search for this author inPubMed Google Scholar * Sanford D Markowitz View author publications You can also search for this author inPubMed Google Scholar * Martina L Veigl View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Eshleman, J., Donover, P., Littman, S. _et al._ Increased transversions in a novel mutator colon cancer cell line. _Oncogene_ 16, 1125–1130 (1998). https://doi.org/10.1038/sj.onc.1201629 Download citation * Received: 18 June 1997 * Revised: 07 October 1997 * Accepted: 07 October 1997 * Published: 10 March 1998 * Issue Date: 05 March 1998 * DOI: https://doi.org/10.1038/sj.onc.1201629 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * colon cancer * HPRT * mutator phenotype * transversions

ABSTRACT We describe a novel mutator phenotype in the Vaco411 colon cancer cell line which increases the spontaneous mutation rate 10–100-fold over background. This mutator results primarily


in transversion base substitutions which are found infrequently in repair competent cells. Of the four possible types of transversions, only three were principally recovered. Spontaneous


mutations recovered also included transitions and large deletions, but very few frameshifts were recovered. When compared to known mismatch repair defective colon cancer mutators, the


distribution of mutations in Vaco411 is significantly different. Consistent with this difference, Vaco411 extracts are proficient in assays of mismatch repair. The Vaco411 mutator appears to


be novel, and is not an obvious human homologue of any of the previously characterized bacterial or yeast transversion phenotypes. Several hypotheses by which this mutator may produce


transversions are presented. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your


institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access


to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our


FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS INHERITED _MUTYH_ MUTATIONS CAUSE ELEVATED SOMATIC MUTATION RATES AND DISTINCTIVE MUTATIONAL SIGNATURES IN NORMAL


HUMAN CELLS Article Open access 08 July 2022 RATE VOLATILITY AND ASYMMETRIC SEGREGATION DIVERSIFY MUTATION BURDEN IN CELLS WITH MUTATOR ALLELES Article Open access 04 January 2021 PERVASIVE


LESION SEGREGATION SHAPES CANCER GENOME EVOLUTION Article 24 June 2020 AUTHOR INFORMATION Author notes * James R Eshleman Present address: Department of Pathology, Ross 632, AUTHORS AND


AFFILIATIONS * Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, Suite 200, UCRC II, 11001 Cedar Road, Cleveland, 44106, Ohio, USA James R


Eshleman * Department of Medicine, University Hospitals of Cleveland and Case Western Reserve University, Suite 200, UCRC II, 11001 Cedar Road, Cleveland, 44106, Ohio, USA P Scott Donover, 


Sandra E Swinler, James D Lutterbaugh, James KV Willson, W David Sedwick & Sanford D Markowitz * Department of General Medical Sciences and Ireland Cancer Center, University Hospitals of


Cleveland and Case Western Reserve University, Suite 200, UCRC II, 11001 Cedar Road, Cleveland, 44106, Ohio, USA Martina L Veigl * Department of Biochemistry and Howard Hughes Medical


Institute, Nanaline Duke Building, Durham, 27710, North Carolina, USA Guo-Min Li & Paul Modrich * Department of Medicine-Oncology, Duke University Medical Center, Nanaline Duke Building,


Durham, 27710, North Carolina, USA Susan J Littman * Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, 21205, Maryland, USA James R Eshleman * Department of Pathology,


University of Kentucky Medical Center, Lexington, 40536, Kentucky, USA Guo-Min Li Authors * James R Eshleman View author publications You can also search for this author inPubMed Google


Scholar * P Scott Donover View author publications You can also search for this author inPubMed Google Scholar * Susan J Littman View author publications You can also search for this author


inPubMed Google Scholar * Sandra E Swinler View author publications You can also search for this author inPubMed Google Scholar * Guo-Min Li View author publications You can also search for


this author inPubMed Google Scholar * James D Lutterbaugh View author publications You can also search for this author inPubMed Google Scholar * James KV Willson View author publications You


can also search for this author inPubMed Google Scholar * Paul Modrich View author publications You can also search for this author inPubMed Google Scholar * W David Sedwick View author


publications You can also search for this author inPubMed Google Scholar * Sanford D Markowitz View author publications You can also search for this author inPubMed Google Scholar * Martina


L Veigl View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Eshleman,


J., Donover, P., Littman, S. _et al._ Increased transversions in a novel mutator colon cancer cell line. _Oncogene_ 16, 1125–1130 (1998). https://doi.org/10.1038/sj.onc.1201629 Download


citation * Received: 18 June 1997 * Revised: 07 October 1997 * Accepted: 07 October 1997 * Published: 10 March 1998 * Issue Date: 05 March 1998 * DOI: https://doi.org/10.1038/sj.onc.1201629


SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to


clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * colon cancer * HPRT * mutator phenotype * transversions