Type I Transforming Growth Factor β Receptor Maps to 9q22 and Exhibits a Polymorphism and a Rare Variant within a Polyalanine Tract

Pasche, Boris; Luo, Yan; Rao, Pulivarthi H.; Nimer, Stephen D.; Dmitrovsky, Ethan; Caron, Philip; Luzzatto, Lucio; Offit, Kenneth; Cordon-Cardo, Carlos; Renault, Béatrice; Satagopan, Jaya M.; Murty, Vundavalli V. V. S.; Massagué, Joan

Article navigation

Articles| July 01 1998

Type I Transforming Growth Factor β Receptor Maps to 9q22 and Exhibits a Polymorphism and a Rare Variant within a Polyalanine Tract^¹

Boris Pasche;

Boris Pasche

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Yan Luo;

Yan Luo

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Pulivarthi H. Rao;

Pulivarthi H. Rao

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Stephen D. Nimer;

Stephen D. Nimer

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Ethan Dmitrovsky;

Ethan Dmitrovsky

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Philip Caron;

Philip Caron

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Lucio Luzzatto;

Lucio Luzzatto

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Kenneth Offit;

Kenneth Offit

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Carlos Cordon-Cardo;

Carlos Cordon-Cardo

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Béatrice Renault;

Béatrice Renault

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Jaya M. Satagopan;

Jaya M. Satagopan

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Vundavalli V. V. S. Murty;

Vundavalli V. V. S. Murty

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Joan Massagué

Cell Biology Program [B. P., Y. L., P. H. R., J. M.], Department of Medicine [B. P., S. D. N., E. D., P. C.], Department of Human Genetics [L. L., K. O.], Department of Pathology [C. C.-C.], Department of Epidemiology and Biostatistics [J. M. S.], and Howard Hughes Medical Institute [J. M.], Memorial Sloan-Kettering Cancer Center

,

New York, New York 10021

;

Department of Molecular Genetics, Albert Einstein College of Medicine

,

Bronx, New York 10461 [B. R.]

; and

Department of Pathology, College of Physicians and Surgeons of Columbia University

,

New York, New York 10021 [V. V. V. S. M.]

Search for other works by this author on:

This Site

PubMed

Google Scholar

Author & Article Information

²

To whom requests for reprints should be addressed, at Memorial Sloan-Kettering Cancer Center, Box 116, 1275 York Avenue, New York, NY 10021. Phone: (212) 639-8975; Fax: (212) 717-3298; E-mail: [email protected].

Received: April 09 1998

Accepted: May 13 1998

Online ISSN: 1538-7445

Print ISSN: 0008-5472

1998

American Association for Cancer Research, Inc.

Cancer Res (1998) 58 (13): 2727–2732.

Abstract

In a search for mutations of the type I transforming growth factor β receptor (TβR-I), we mapped the gene to 9q22 and found a common polymorphism [TβR-I(6A)] and a rare variant [TβR-I(10A)] of TβR-I, causing an in-frame deletion of three alanines and an in-frame insertion of one alanine, respectively, in the receptor's extracellular domain. The biological relevance of the polymorphism TβR-I(6A) was investigated. When TβR-I(6A) was transiently transfected into TβR-I-deficient cells, the growth-inhibitory effects of transforming growth factor β were restored. TβR-I(6A) and TβR-I(10A) frequency were assessed in 108 tumor samples and 80 nontumor samples from patients with a diagnosis of cancer, as well as in 118 normal blood donors of comparable ethnic composition. The frequency of TβR-I(6A) heterozygotes was fairly similar in normal blood donors (8%), in nontumor DNA of patients with a diagnosis of cancer (10%), and in tumor samples (14%). However, the frequency of TβR-I(6A) homozygotes among nontumor (4%) and tumor (8%) samples obtained from patients with a diagnosis of cancer was higher than that predicted by the Hardy-Weinberg law. The clinical and biological significance of TβR-I(6A) homozygosity needs to be further investigated.

¹

This work was supported by NIH Grants K12 CA01712-04 (to B. P.), CA34610 (to J. M.), DK43025 (to S. D. N.), and CA 54494 and CA 62275 (to E. D.); by the DeWitt Wallace Foundations (to S. D. N.); and by a Cancer Center Grant to Memorial Sloan-Kettering Cancer Center. J. M. is a Howard Hughes Medical Institute Investigator.

This content is only available via PDF.

1998

American Association for Cancer Research, Inc.

Type I Transforming Growth Factor β Receptor Maps to 9q22 and Exhibits a Polymorphism and a Rare Variant within a Polyalanine Tract^¹

Abstract

Citing articles via

Email alerts

AACR Journals

Type I Transforming Growth Factor β Receptor Maps to 9q22 and Exhibits a Polymorphism and a Rare Variant within a Polyalanine Tract1

Abstract

Citing articles via

Email alerts

AACR Journals

This Feature Is Available To Subscribers Only

Type I Transforming Growth Factor β Receptor Maps to 9q22 and Exhibits a Polymorphism and a Rare Variant within a Polyalanine Tract^¹