Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants

Cathy C. Laurie, Cecelia A. Laurie, Stephanie A. Smoley, Erin E. Carlson, Ian Flinn, Brooke L. Fridley, Harvey A. Greisman, John G. Gribben, Diane F. Jelinek, Sarah C. Nelson, Elisabeth M. Paietta, Dan Schaid, Zhuoxin Sun, Martin S. Tallman, Richard Weinshilboum, Neil E. Kay, Tait D. Shanafelt

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Pretherapy patients with chronic lymphocytic leukemia (CLL) from US Intergroup trial E2997 were analyzed with single nucleotide polymorphism microarrays to detect acquired chromosomal anomalies. The four CLL-typical anomalies (11q-, +12, 13q-, and 17p-) were found at expected frequencies. Acquired anomalies in other regions account for 70% of the total detected anomalies, and their number per participant has a significant effect on progression-free survival after adjusting for the effects of 17p- (and other covariates). These results were compared with those from a previous study of more than 50,000 participants from the GENEVA consortium of genome-wide association studies, which analyzed individuals with a variety of medical conditions and healthy controls. The percentage of individuals with acquired anomalies is vastly different between the two studies (GENEVA 0.8%; E2997 80%). The composition of the anomalies also differs, with GENEVA having a higher percentage of acquired uniparental disomies and a lower percentage of deletions. The four common CLL anomalies are among the most frequent in GENEVA participants, some of whom may have CLL-precursor conditions or early stages of CLL. However, the patients from E2997 (and other studies of symptomatic CLL) have recurrent acquired anomalies that were not found in GENEVA participants, thus identifying genomic changes that may be unique to symptomatic stages of CLL.

Original languageEnglish (US)
Pages (from-to)19-30
Number of pages12
JournalCancer genetics
Volume207
Issue number1-2
DOIs
StatePublished - 2014

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B-Cell Chronic Lymphocytic Leukemia
Uniparental Disomy
Genome-Wide Association Study
Disease-Free Survival
Single Nucleotide Polymorphism

Keywords

  • Cancer precursor condition
  • Chromosomal aberration
  • Chromosomal mosaic
  • Chronic lymphocytic leukemia
  • Cytogenetics

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Laurie, C. C., Laurie, C. A., Smoley, S. A., Carlson, E. E., Flinn, I., Fridley, B. L., ... Shanafelt, T. D. (2014). Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants. Cancer genetics, 207(1-2), 19-30. https://doi.org/10.1016/j.cancergen.2014.01.004

Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants. / Laurie, Cathy C.; Laurie, Cecelia A.; Smoley, Stephanie A.; Carlson, Erin E.; Flinn, Ian; Fridley, Brooke L.; Greisman, Harvey A.; Gribben, John G.; Jelinek, Diane F.; Nelson, Sarah C.; Paietta, Elisabeth M.; Schaid, Dan; Sun, Zhuoxin; Tallman, Martin S.; Weinshilboum, Richard; Kay, Neil E.; Shanafelt, Tait D.

In: Cancer genetics, Vol. 207, No. 1-2, 2014, p. 19-30.

Research output: Contribution to journalArticle

Laurie, CC, Laurie, CA, Smoley, SA, Carlson, EE, Flinn, I, Fridley, BL, Greisman, HA, Gribben, JG, Jelinek, DF, Nelson, SC, Paietta, EM, Schaid, D, Sun, Z, Tallman, MS, Weinshilboum, R, Kay, NE & Shanafelt, TD 2014, 'Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants', Cancer genetics, vol. 207, no. 1-2, pp. 19-30. https://doi.org/10.1016/j.cancergen.2014.01.004
Laurie, Cathy C. ; Laurie, Cecelia A. ; Smoley, Stephanie A. ; Carlson, Erin E. ; Flinn, Ian ; Fridley, Brooke L. ; Greisman, Harvey A. ; Gribben, John G. ; Jelinek, Diane F. ; Nelson, Sarah C. ; Paietta, Elisabeth M. ; Schaid, Dan ; Sun, Zhuoxin ; Tallman, Martin S. ; Weinshilboum, Richard ; Kay, Neil E. ; Shanafelt, Tait D. / Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants. In: Cancer genetics. 2014 ; Vol. 207, No. 1-2. pp. 19-30.
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abstract = "Pretherapy patients with chronic lymphocytic leukemia (CLL) from US Intergroup trial E2997 were analyzed with single nucleotide polymorphism microarrays to detect acquired chromosomal anomalies. The four CLL-typical anomalies (11q-, +12, 13q-, and 17p-) were found at expected frequencies. Acquired anomalies in other regions account for 70{\%} of the total detected anomalies, and their number per participant has a significant effect on progression-free survival after adjusting for the effects of 17p- (and other covariates). These results were compared with those from a previous study of more than 50,000 participants from the GENEVA consortium of genome-wide association studies, which analyzed individuals with a variety of medical conditions and healthy controls. The percentage of individuals with acquired anomalies is vastly different between the two studies (GENEVA 0.8{\%}; E2997 80{\%}). The composition of the anomalies also differs, with GENEVA having a higher percentage of acquired uniparental disomies and a lower percentage of deletions. The four common CLL anomalies are among the most frequent in GENEVA participants, some of whom may have CLL-precursor conditions or early stages of CLL. However, the patients from E2997 (and other studies of symptomatic CLL) have recurrent acquired anomalies that were not found in GENEVA participants, thus identifying genomic changes that may be unique to symptomatic stages of CLL.",
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AU - Laurie, Cecelia A.

AU - Smoley, Stephanie A.

AU - Carlson, Erin E.

AU - Flinn, Ian

AU - Fridley, Brooke L.

AU - Greisman, Harvey A.

AU - Gribben, John G.

AU - Jelinek, Diane F.

AU - Nelson, Sarah C.

AU - Paietta, Elisabeth M.

AU - Schaid, Dan

AU - Sun, Zhuoxin

AU - Tallman, Martin S.

AU - Weinshilboum, Richard

AU - Kay, Neil E.

AU - Shanafelt, Tait D.

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