MET receptor sequence variants R970C and T992I lack transforming capacity

Jeffrey Tyner, Luke B. Fletcher, Ellen Q. Wang, Wayne F. Yang, Michael L. Rutenberg-Schoenberg, Carol Beadling, Motomi (Tomi) Mori, Michael Heinrich, Michael W. Deininger, Brian Druker, Marc Loriaux

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

High-throughput sequencing promises to accelerate the discovery of sequence variants, but distinguishing oncogenic mutations from irrelevant "passenger" mutations remains a major challenge. Here we present an analysis of two sequence variants of the MET receptor (hepatocyte growth factor receptor) R970C and T992I (also designated R988C and T1010I). Previous reports indicated that these sequence variants are transforming and contribute to oncogenesis. We screened patients with chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), colorectal cancer, endometrial cancer, thyroid cancer, or melanoma, as well as individuals without cancer, and found these variants at low frequencies in most cohorts, including normal individuals. No evidence of increased phosphorylation or transformative capacity by either sequence variant was found. Because small-molecule inhibitors for MET are currently in development, it will be important to distinguish between oncogenic sequence variants and rare singlenucleotide polymorphisms to avoid the use of unnecessary, and potentially toxic, cancer therapy agents.

Original languageEnglish (US)
Pages (from-to)6233-6237
Number of pages5
JournalCancer Research
Volume70
Issue number15
DOIs
StatePublished - Aug 1 2010

Fingerprint

Thyroid Neoplasms
Leukemia, Myelomonocytic, Chronic
Proto-Oncogene Proteins c-met
Mutation
Poisons
B-Cell Chronic Lymphocytic Leukemia
Endometrial Neoplasms
Acute Myeloid Leukemia
Sequence Analysis
Colorectal Neoplasms
Melanoma
Neoplasms
Carcinogenesis
Phosphorylation
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

MET receptor sequence variants R970C and T992I lack transforming capacity. / Tyner, Jeffrey; Fletcher, Luke B.; Wang, Ellen Q.; Yang, Wayne F.; Rutenberg-Schoenberg, Michael L.; Beadling, Carol; Mori, Motomi (Tomi); Heinrich, Michael; Deininger, Michael W.; Druker, Brian; Loriaux, Marc.

In: Cancer Research, Vol. 70, No. 15, 01.08.2010, p. 6233-6237.

Research output: Contribution to journalArticle

Tyner, Jeffrey ; Fletcher, Luke B. ; Wang, Ellen Q. ; Yang, Wayne F. ; Rutenberg-Schoenberg, Michael L. ; Beadling, Carol ; Mori, Motomi (Tomi) ; Heinrich, Michael ; Deininger, Michael W. ; Druker, Brian ; Loriaux, Marc. / MET receptor sequence variants R970C and T992I lack transforming capacity. In: Cancer Research. 2010 ; Vol. 70, No. 15. pp. 6233-6237.
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