Abstract
In the pediatric cancer alveolar rhabdomyosarcoma, characteristic t(2;13)(q35;q14) or variant t(1;13)(p36;q14) chromosomal translocations generate PAX3-FKHR or PAX7-FKHR fusion genes. Using fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction and quantitative Southern blot analyses, we demonstrate that these fusion genes are amplified in 20% of fusion-positive tumors. In particular, we found in vivo amplification of these fusions in one of 22 PAX3-FKHR-positive cases and five of seven PAX7-FKHR-positive cases. These findings indicate that translocation and amplification can occur sequentially in a cancer to alter both the structure and copy number of a gene and thereby activate oncogenic activity by complementary mechanisms.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Base Sequence
-
DNA, Neoplasm / analysis
-
DNA, Neoplasm / genetics
-
DNA-Binding Proteins / genetics*
-
Forkhead Box Protein O1
-
Forkhead Transcription Factors
-
Gene Amplification*
-
Homeodomain Proteins*
-
Humans
-
Molecular Sequence Data
-
Muscle Proteins / genetics
-
Nerve Tissue Proteins / genetics
-
PAX3 Transcription Factor
-
PAX7 Transcription Factor
-
Paired Box Transcription Factors
-
RNA, Neoplasm / analysis
-
Rhabdomyosarcoma, Alveolar / genetics*
-
Transcription Factors / genetics*
-
Translocation, Genetic / genetics*
Substances
-
DNA, Neoplasm
-
DNA-Binding Proteins
-
FOXO1 protein, human
-
Forkhead Box Protein O1
-
Forkhead Transcription Factors
-
Homeodomain Proteins
-
Muscle Proteins
-
Nerve Tissue Proteins
-
PAX3 Transcription Factor
-
PAX3 protein, human
-
PAX7 Transcription Factor
-
PAX7 protein, human
-
Paired Box Transcription Factors
-
RNA, Neoplasm
-
Transcription Factors
-
Pax3 protein, mouse