Abstract
In addition to the intracellular sorting of lysosomal enzymes, the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) plays a critical role in regulating the bioavailability of extracellular proteolytic enzymes and growth factors. It has also been shown to be mutated in a number of human cancers, and to suppress cancer cell growth. The purpose of this study was to determine if the M6P/IGF2R is mutated in lung cancer, a leading cause of cancer death worldwide. Archival pathology specimens were obtained on 22 patients with newly diagnosed, untreated squamous cell carcinoma of the lung. Two polymorphisms in the 3'-untranslated region of the M6P/IGF2R were used to screen lung tumors for loss of heterozygosity (LOH) by PCR amplification of DNA. Nineteen of 22 (86%) patients were informative (heterozygous), and 11/19 (58%) squamous cell carcinomas of the lung had LOH at the M6P/IGF2R locus. The remaining allele in 6/11 (55%) LOH patients contained mutations in either the mannose 6-phosphate or the IGF2 binding domain of the M6P/ IGF2R. Thus, the M6P/IGF2R is mutated frequently in squamous cell carcinoma of the lung, providing further support for its function as a tumor suppressor.
Original language | English (US) |
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Pages (from-to) | 1572-1578 |
Number of pages | 7 |
Journal | Oncogene |
Volume | 19 |
Issue number | 12 |
DOIs | |
State | Published - Mar 16 2000 |
Externally published | Yes |
Keywords
- Loss of heterozygosity
- Lung cancer
- M6P/IGF2R
- Mutation
- Tumor suppressor
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research