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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2854-2861
A Deletion in the Gene for Transforming Growth Factor  Type I
Receptor Abolishes Growth Regulation by Transforming Growth Factor
in a Cutaneous T-Cell Lymphoma
William P. Schiemann,
Walther M. Pfeifer,
Edi Levi,
Marshall E. Kadin, and
Harvey F. Lodish
From the Whitehead Institute for Biomedical Research, Cambridge; the
Department of Pathology, Beth Israel Deaconess Medical Center and
Harvard Medical School, Boston; and the Department of Biology,
Massachusetts Institute of Technology, Cambridge, MA.
Spontaneous regression of skin lesions is characteristic of
lymphomatoid papulosis (LyP), a clonal cutaneous lymphoproliferative disorder. A minority of LyP patients progress to anaplastic large cell
lymphoma (ALCL) in which skin lesions no longer regress and extracutaneous dissemination often occurs. In 1 such case, we developed
a tumor cell line, JK cells, and show that these cells are resistant to
the growth inhibitory effects of transforming growth factor  (TGF-) due to the loss of cell surface expression of the TGF-
type I receptor (TR-I). Reverse transcriptase-polymerase chain
reaction (RT-PCR) and sequencing of JK cell TR-I cDNA clones identified a deletion that spanned the last 178 bp of exon 1, including
the initiating methionine. Hybridization of a radiolabeled fragment
internal to the deletion was detected in the genomes of
TGF--responsive cells, but not in JK cells, indicating that they
contain no wild-type TR-I gene. PCR primers that flanked the deleted
TR-I region amplified a single band from JK cell genomic DNA that
lacked the last 178 bp of exon 1 and all of the  5 kb of intron 1. This JK cell-specific genomic TR-I PCR product was distinct from
products amplified from TGF--responsive cells and was also readily
detected in tumor biopsies obtained before the establishment of the JK
cell line. Our results identify the first inactivating mutation in
TR-I gene in a human lymphoma that renders it insensitive to growth
inhibition by TGF-.
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