MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines

David H.F. Teng, Rong Hu, Huai Lin, Thaylon Davis, Diana Iliev, Cheryl Frye, Brad Swedlund, Kipp L. Hansen, Vickie L. Vinson, Kathryn L. Gumpper, Lee Ellis, Adel El-Naggar, Marsha Frazier, Samar Jasser, Lauren A. Langford, Jeff Lee, Gordon Mills, Mark A. Pershouse, Raphael E. Pollack, Carmen TornosPatricia Troncoso, W. K.Alfred Yung, Gregory Fujii, Amy Berson, Robert Bookstein, Joseph B. Bolen, Scan V. Tavtigian, Peter A. Steck

Research output: Contribution to journalArticle

443 Citations (Scopus)

Abstract

A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (-23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (-16%) of the lines, including these derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (- 145) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.

Original languageEnglish (US)
Pages (from-to)5221-5225
Number of pages5
JournalCancer Research
Volume57
Issue number23
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

Tumor Cell Line
Mutation
Loss of Heterozygosity
Neoplasms
Glioblastoma
Prostate
Melanoma
Breast
Cell Line
Chromosomes, Human, Pair 9
Pseudogenes
Nonsense Codon
Submandibular Gland
Astrocytoma
Human Chromosomes
Tumor Suppressor Genes
Glioma
Genes
Testis
Leukemia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Teng, D. H. F., Hu, R., Lin, H., Davis, T., Iliev, D., Frye, C., ... Steck, P. A. (1997). MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Research, 57(23), 5221-5225.

MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. / Teng, David H.F.; Hu, Rong; Lin, Huai; Davis, Thaylon; Iliev, Diana; Frye, Cheryl; Swedlund, Brad; Hansen, Kipp L.; Vinson, Vickie L.; Gumpper, Kathryn L.; Ellis, Lee; El-Naggar, Adel; Frazier, Marsha; Jasser, Samar; Langford, Lauren A.; Lee, Jeff; Mills, Gordon; Pershouse, Mark A.; Pollack, Raphael E.; Tornos, Carmen; Troncoso, Patricia; Yung, W. K.Alfred; Fujii, Gregory; Berson, Amy; Bookstein, Robert; Bolen, Joseph B.; Tavtigian, Scan V.; Steck, Peter A.

In: Cancer Research, Vol. 57, No. 23, 01.12.1997, p. 5221-5225.

Research output: Contribution to journalArticle

Teng, DHF, Hu, R, Lin, H, Davis, T, Iliev, D, Frye, C, Swedlund, B, Hansen, KL, Vinson, VL, Gumpper, KL, Ellis, L, El-Naggar, A, Frazier, M, Jasser, S, Langford, LA, Lee, J, Mills, G, Pershouse, MA, Pollack, RE, Tornos, C, Troncoso, P, Yung, WKA, Fujii, G, Berson, A, Bookstein, R, Bolen, JB, Tavtigian, SV & Steck, PA 1997, 'MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines', Cancer Research, vol. 57, no. 23, pp. 5221-5225.
Teng DHF, Hu R, Lin H, Davis T, Iliev D, Frye C et al. MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Research. 1997 Dec 1;57(23):5221-5225.
Teng, David H.F. ; Hu, Rong ; Lin, Huai ; Davis, Thaylon ; Iliev, Diana ; Frye, Cheryl ; Swedlund, Brad ; Hansen, Kipp L. ; Vinson, Vickie L. ; Gumpper, Kathryn L. ; Ellis, Lee ; El-Naggar, Adel ; Frazier, Marsha ; Jasser, Samar ; Langford, Lauren A. ; Lee, Jeff ; Mills, Gordon ; Pershouse, Mark A. ; Pollack, Raphael E. ; Tornos, Carmen ; Troncoso, Patricia ; Yung, W. K.Alfred ; Fujii, Gregory ; Berson, Amy ; Bookstein, Robert ; Bolen, Joseph B. ; Tavtigian, Scan V. ; Steck, Peter A. / MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. In: Cancer Research. 1997 ; Vol. 57, No. 23. pp. 5221-5225.
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abstract = "A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (10{\%}) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (-23{\%}). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (-16{\%}) of the lines, including these derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (- 145) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.",
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AU - Teng, David H.F.

AU - Hu, Rong

AU - Lin, Huai

AU - Davis, Thaylon

AU - Iliev, Diana

AU - Frye, Cheryl

AU - Swedlund, Brad

AU - Hansen, Kipp L.

AU - Vinson, Vickie L.

AU - Gumpper, Kathryn L.

AU - Ellis, Lee

AU - El-Naggar, Adel

AU - Frazier, Marsha

AU - Jasser, Samar

AU - Langford, Lauren A.

AU - Lee, Jeff

AU - Mills, Gordon

AU - Pershouse, Mark A.

AU - Pollack, Raphael E.

AU - Tornos, Carmen

AU - Troncoso, Patricia

AU - Yung, W. K.Alfred

AU - Fujii, Gregory

AU - Berson, Amy

AU - Bookstein, Robert

AU - Bolen, Joseph B.

AU - Tavtigian, Scan V.

AU - Steck, Peter A.

PY - 1997/12/1

Y1 - 1997/12/1

N2 - A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (-23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (-16%) of the lines, including these derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (- 145) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.

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