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DPC4 gene in various tumor types
M Schutte1, R H Hruban, L Hedrick
1Gepartment of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196, USA.
Abstract:
We recently identified a novel tumor-suppressor gene, DPC4, at chromosome 18q21.1 and found that both alleles of DPC4 were inactivated in nearly one-half of the pancreatic carcinomas. Here, we analyzed 338 tumors, originating from 12 distinct anatomic sites, for alterations in the DPC4 gene. Sixty-four specimens were selected for the presence of the allelic loss of 18q and were further analyzed for DPC4 sequence alterations. An alteration of the DPC4 gene sequence was identified in one of eight breast carcinomas and one of eight ovarian carcinomas. These results indicate that whereas DPC4 inactivation is prevalent in pancreatic carcinoma (48%), it is distinctly uncommon (< 10%) in the other tumor types examined. The tissue restriction of alterations in DPC4, as in many other tumor-suppressor genes, emphasizes the complexity of rate-limiting checkpoints in human tumorigenesis.
Insights
The DPC4 tumor-suppressor gene is frequently inactivated in pancreatic cancer. Alterations in DPC4 are uncommon in other cancer types, highlighting tissue-specific roles in tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- A novel tumor-suppressor gene, DPC4, located at chromosome 18q21.1, was previously identified.
- Both alleles of DPC4 were found to be inactivated in approximately 50% of pancreatic carcinomas.
Purpose of the Study:
- To investigate alterations in the DPC4 gene across a diverse range of tumor types.
- To determine the prevalence of DPC4 gene inactivation in various human cancers.
Main Methods:
- Analysis of 338 tumors from 12 different anatomic sites for DPC4 gene alterations.
- Targeted sequencing of DPC4 in 64 specimens exhibiting 18q allelic loss.
Main Results:
- DPC4 inactivation was identified in 48% of pancreatic carcinomas.
- Alterations in DPC4 were found in one of eight breast carcinomas and one of eight ovarian carcinomas.
- DPC4 inactivation was observed in less than 10% of other tumor types analyzed.
Conclusions:
- DPC4 inactivation is a prevalent event in pancreatic cancer but rare in other examined tumor types.
- The tissue-specific nature of DPC4 alterations suggests a complex role in human tumorigenesis.
- This highlights the intricate rate-limiting checkpoints involved in cancer development.