BREAKPOINT CHARACTERIZATION OF THE RET/PTC ONCOGENE IN HUMAN PAPILLARY THYROID-CARCINOMA

被引:48
作者
SMANIK, PA
FURMINGER, TL
MAZZAFERRI, EL
JHIANG, SM
机构
[1] OHIO STATE UNIV,DEPT PHYSIOL,COLUMBUS,OH 43210
[2] OHIO STATE UNIV,DEPT INTERNAL MED,COLUMBUS,OH 43210
关键词
D O I
10.1093/hmg/4.12.2313
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The ret/PTC oncogene, a rearranged form of the ret proto-oncogene (c-ret), has been detected specifically in a minority of papillary thyroid carcinomas, Three forms of the ret/PTC oncogene have been identified; the two most common forms, ret/PTC-1 and ret/PTC-3, both result from a paracentric inversion of the long arm of chromosome 10. In this study, we have successfully amplified the chimeric introns resulting from these inversions, ranging from 1.4 to 10 kb, from four of five tumors known to contain the ret/PTC-1 oncogene (where c-ret rearranges with the H4 gene), and from 1/1 tumor containing the ret/PTC-3 oncogene (where c-ret rearranges with the ele1 gene). We localized the breakpoints within the chimeric introns using nested PCR, and determined the exact nucleotide sequence at the breakpoint for each tumor. Our results indicate that the breakpoints in c-ret occur at sites distributed across intron 11, while breaks in H4 intron 1 appear to occur more frequently at the 5'-end of the intron. Interestingly, in all tumors that we investigated, the breakpoints occurred at sites of two or three nucleotide matches between the contributing germline sequences. In summary, we describe a simple, convenient way to investigate the ret/PTC breakpoints, and have revealed several common features of the breakpoints which warrant further investigation.
引用
收藏
页码:2313 / 2318
页数:6
相关论文
共 32 条
[1]   MECHANISM OF THE T(14-18) CHROMOSOMAL TRANSLOCATION - STRUCTURAL-ANALYSIS OF BOTH DERIVATIVE-14 AND DERIVATIVE-18 RECIPROCAL PARTNERS [J].
BAKHSHI, A ;
WRIGHT, JJ ;
GRANINGER, W ;
SETO, M ;
OWENS, J ;
COSSMAN, J ;
JENSEN, JP ;
GOLDMAN, P ;
KORSMEYER, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (08) :2396-2400
[2]  
BONGARZONE I, 1989, ONCOGENE, V4, P1457
[3]   MOLECULAR CHARACTERIZATION OF A THYROID TUMOR-SPECIFIC TRANSFORMING SEQUENCE FORMED BY THE FUSION OF RET TYROSINE KINASE AND THE REGULATORY SUBUNIT RI-ALPHA OF CYCLIC AMP-DEPENDENT PROTEIN KINASE-A [J].
BONGARZONE, I ;
MONZINI, N ;
BORRELLO, MG ;
CARCANO, C ;
FERRARESI, G ;
ARIGHI, E ;
MONDELLINI, P ;
DELLAPORTA, G ;
PIEROTTI, MA .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (01) :358-366
[4]  
BONGARZONE I, 1994, CANCER RES, V54, P2979
[5]  
BUTTI MG, EMBL X77860
[6]  
BUTTI MG, EMBL X77859
[7]   CHARACTERIZATION OF THE REARRANGED TPR-MET ONCOGENE BREAKPOINT [J].
DEAN, M ;
PARK, M ;
VANDEWOUDE, GF .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (02) :921-924
[8]   MUTATIONS OF THE RET PROTOONCOGENE IN HIRSCHSPRUNGS-DISEASE [J].
EDERY, P ;
LYONNET, S ;
MULLIGAN, LM ;
PELET, A ;
DOW, E ;
ABEL, L ;
HOLDER, S ;
NIHOULFEKETE, C ;
PONDER, BAJ ;
MUNNICH, A .
NATURE, 1994, 367 (6461) :378-380
[9]  
FRANCESCHI S, 1993, CRIT REV ONCOGENESIS, V4, P25
[10]   SPLICE SITE CHOICE AND SPLICING EFFICIENCY ARE POSITIVELY INFLUENCED BY PREMESSENGER RNA INTRAMOLECULAR BASE-PAIRING IN YEAST [J].
GOGUEL, V ;
ROSBASH, M .
CELL, 1993, 72 (06) :893-901