RET/PTC rearrangement occurring in primary peritoneal carcinoma.
RET/PTC rearrangements are initiating events in the development of a significant proportion of papillary thyroid carcinomas. Activated RET/PTC mutations are thought to be restricted to thyroid disease, but this study proposes that these events may also occur in nonthyroid tumors. A total of 57 nonthyroid papillary tumors were examined for RET/PTC rearrangements using interphase fluorescence in situ hybridization, Taqman reverse transcriptase polymerase chain reaction, and immunohistochemistry. Taqman single nucleotide polymorphism detection was used to analyze for expression of mutated BRAF T1799A. In all, 20% (3/15) of primary peritoneal carcinoma had detectable RET/PTC1 rearrangements by all 3 methodologies. A further case of similar histotype had an alternate RET/ PTC rearrangement. No RET/PTC1 rearrangements were detected in the remaining tumor cohort. All 57 tumors were homozygous for wild-type BRAF. The results indicate that RET/PTC rearrangements occur in a small subset of nonthyroid papillary tumors. These rearrangements may not be directly implicated in tumor growth; rather representing "passenger" mutations reflecting RET instability in secondary tumor subclones.
Flavin
Richard
R
Department of Histopathology, Trinity College Medical School, Dublin, Ireland. flavinr@tcd.ie
Jackl
Gerhard
G
Finn
Stephen
S
Smyth
Paul
P
Ring
Martina
M
O'Regan
Esther
E
Cahill
Susanne
S
Unger
Kristian
K
Denning
Karen
K
Jinghuan Li
Aherne
Sinead
S
Tallini
Giovanni
G
Gaffney
Eoin
E
O'Leary
J J
JJ
Zitzelsberger
Horst
H
Sheils
Orla
O
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D015514:Oncogene Proteins, Fusion; D051096:Proto-Oncogene Proteins c-ret; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf