Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia

David A. Sweetser, Andrew J. Peniket, Christina Haaland, Adam A. Blomberg, Yuntian Zhang, Syed Tanweer Zaidi, Farshid Dayyani, Zheng Zhao, Nyla A. Heerema, Jacqueline Boultwood, Gordon W. Dewald, Elisabeth M. Paietta, Marilyn L. Slovak, Cheryl L. Willman, James S. Wainscoat, Irwin D. Bernstein, Sarah B. Daly

Research output: Contribution to journalArticle

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Abstract

Deletion of the long arm of chromosome 9, del(9q), is a recurring chromosomal aberration in acute myeloid leukemia (AML) that is frequently associated with t(8;21). The critical gene products affected by del(9q) are unknown but likely cooperate with the AMLI/ETO fusion gene created by t(8;21) in leukemogenesis. In 43 AML samples with del(9q), we used high-density microsatellite markers to define the commonly deleted region (CDR) to less than 2.4 Mb. We found no homozygous loss at any locus tested. The CDR contains 7 known genes, FRMD3, UBQLNI, GKAP42, KIF27, HNRPK, SLC28A3, and NTRK2, and 4 novel genes, RASEF, C9orf103, C9orf64, and C9orf76. In addition, TLE1 and TLE4 are adjacent to the CDR. We performed a comprehensive mutational analysis of the coding regions of all these genes. No sequence variations absent in normal controls were seen in more than a single del(9q) AML sample. Expression of 7 of the 10 genes examined was significantly down-regulated in del(19q)AML as compared with the CD34-purified progenitors from normal individuals, a pattern distinct from that seen in AML samples with a normal karyotype. The results of our studies are consistent with a model of tumor suppression mediated by haploinsufficiency of critical genes in del(9q) AML.

Original languageEnglish (US)
Pages (from-to)279-291
Number of pages13
JournalGenes Chromosomes and Cancer
Volume44
Issue number3
DOIs
StatePublished - Nov 2005
Externally publishedYes

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Tumor Suppressor Genes
Acute Myeloid Leukemia
Genes
Haploinsufficiency
Chromosomes, Human, Pair 9
Gene Fusion
Karyotype
Chromosome Aberrations
Microsatellite Repeats
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia. / Sweetser, David A.; Peniket, Andrew J.; Haaland, Christina; Blomberg, Adam A.; Zhang, Yuntian; Zaidi, Syed Tanweer; Dayyani, Farshid; Zhao, Zheng; Heerema, Nyla A.; Boultwood, Jacqueline; Dewald, Gordon W.; Paietta, Elisabeth M.; Slovak, Marilyn L.; Willman, Cheryl L.; Wainscoat, James S.; Bernstein, Irwin D.; Daly, Sarah B.

In: Genes Chromosomes and Cancer, Vol. 44, No. 3, 11.2005, p. 279-291.

Research output: Contribution to journalArticle

Sweetser, DA, Peniket, AJ, Haaland, C, Blomberg, AA, Zhang, Y, Zaidi, ST, Dayyani, F, Zhao, Z, Heerema, NA, Boultwood, J, Dewald, GW, Paietta, EM, Slovak, ML, Willman, CL, Wainscoat, JS, Bernstein, ID & Daly, SB 2005, 'Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia', Genes Chromosomes and Cancer, vol. 44, no. 3, pp. 279-291. https://doi.org/10.1002/gcc.20236
Sweetser, David A. ; Peniket, Andrew J. ; Haaland, Christina ; Blomberg, Adam A. ; Zhang, Yuntian ; Zaidi, Syed Tanweer ; Dayyani, Farshid ; Zhao, Zheng ; Heerema, Nyla A. ; Boultwood, Jacqueline ; Dewald, Gordon W. ; Paietta, Elisabeth M. ; Slovak, Marilyn L. ; Willman, Cheryl L. ; Wainscoat, James S. ; Bernstein, Irwin D. ; Daly, Sarah B. / Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia. In: Genes Chromosomes and Cancer. 2005 ; Vol. 44, No. 3. pp. 279-291.
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abstract = "Deletion of the long arm of chromosome 9, del(9q), is a recurring chromosomal aberration in acute myeloid leukemia (AML) that is frequently associated with t(8;21). The critical gene products affected by del(9q) are unknown but likely cooperate with the AMLI/ETO fusion gene created by t(8;21) in leukemogenesis. In 43 AML samples with del(9q), we used high-density microsatellite markers to define the commonly deleted region (CDR) to less than 2.4 Mb. We found no homozygous loss at any locus tested. The CDR contains 7 known genes, FRMD3, UBQLNI, GKAP42, KIF27, HNRPK, SLC28A3, and NTRK2, and 4 novel genes, RASEF, C9orf103, C9orf64, and C9orf76. In addition, TLE1 and TLE4 are adjacent to the CDR. We performed a comprehensive mutational analysis of the coding regions of all these genes. No sequence variations absent in normal controls were seen in more than a single del(9q) AML sample. Expression of 7 of the 10 genes examined was significantly down-regulated in del(19q)AML as compared with the CD34-purified progenitors from normal individuals, a pattern distinct from that seen in AML samples with a normal karyotype. The results of our studies are consistent with a model of tumor suppression mediated by haploinsufficiency of critical genes in del(9q) AML.",
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T1 - Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia

AU - Sweetser, David A.

AU - Peniket, Andrew J.

AU - Haaland, Christina

AU - Blomberg, Adam A.

AU - Zhang, Yuntian

AU - Zaidi, Syed Tanweer

AU - Dayyani, Farshid

AU - Zhao, Zheng

AU - Heerema, Nyla A.

AU - Boultwood, Jacqueline

AU - Dewald, Gordon W.

AU - Paietta, Elisabeth M.

AU - Slovak, Marilyn L.

AU - Willman, Cheryl L.

AU - Wainscoat, James S.

AU - Bernstein, Irwin D.

AU - Daly, Sarah B.

PY - 2005/11

Y1 - 2005/11

N2 - Deletion of the long arm of chromosome 9, del(9q), is a recurring chromosomal aberration in acute myeloid leukemia (AML) that is frequently associated with t(8;21). The critical gene products affected by del(9q) are unknown but likely cooperate with the AMLI/ETO fusion gene created by t(8;21) in leukemogenesis. In 43 AML samples with del(9q), we used high-density microsatellite markers to define the commonly deleted region (CDR) to less than 2.4 Mb. We found no homozygous loss at any locus tested. The CDR contains 7 known genes, FRMD3, UBQLNI, GKAP42, KIF27, HNRPK, SLC28A3, and NTRK2, and 4 novel genes, RASEF, C9orf103, C9orf64, and C9orf76. In addition, TLE1 and TLE4 are adjacent to the CDR. We performed a comprehensive mutational analysis of the coding regions of all these genes. No sequence variations absent in normal controls were seen in more than a single del(9q) AML sample. Expression of 7 of the 10 genes examined was significantly down-regulated in del(19q)AML as compared with the CD34-purified progenitors from normal individuals, a pattern distinct from that seen in AML samples with a normal karyotype. The results of our studies are consistent with a model of tumor suppression mediated by haploinsufficiency of critical genes in del(9q) AML.

AB - Deletion of the long arm of chromosome 9, del(9q), is a recurring chromosomal aberration in acute myeloid leukemia (AML) that is frequently associated with t(8;21). The critical gene products affected by del(9q) are unknown but likely cooperate with the AMLI/ETO fusion gene created by t(8;21) in leukemogenesis. In 43 AML samples with del(9q), we used high-density microsatellite markers to define the commonly deleted region (CDR) to less than 2.4 Mb. We found no homozygous loss at any locus tested. The CDR contains 7 known genes, FRMD3, UBQLNI, GKAP42, KIF27, HNRPK, SLC28A3, and NTRK2, and 4 novel genes, RASEF, C9orf103, C9orf64, and C9orf76. In addition, TLE1 and TLE4 are adjacent to the CDR. We performed a comprehensive mutational analysis of the coding regions of all these genes. No sequence variations absent in normal controls were seen in more than a single del(9q) AML sample. Expression of 7 of the 10 genes examined was significantly down-regulated in del(19q)AML as compared with the CD34-purified progenitors from normal individuals, a pattern distinct from that seen in AML samples with a normal karyotype. The results of our studies are consistent with a model of tumor suppression mediated by haploinsufficiency of critical genes in del(9q) AML.

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