RET rearrangements in post-Chernobyl papillary thyroid carcinomas with a short latency analysed by interphase FISH

Abstract

Tissue samples from 13 post-Chernobyl childhood thyroid tumours that occurred within a short period of time (4 -8 years) after the Chernobyl accident have been investigated by interphase FISH analysis for rearrangements of RET. In all, 77% of cases showed RET/ PTC rearrangements and a distinct intratumoural genetic heterogeneity. The data were compared to findings on 32 post-Chernobyl PTCs that occurred after a longer period of time (9 -12 years) after the accident. In none of the cases from either group were 100% of cells positive for RET rearrangement. In addition, the pattern of RET-positive cells was different in the two groups (short vs longer latency). A significant clustering of aberrant cells could be detected in the long-latency subgroup, whereas the aberrant cells were more homogeneously distributed among the short-latency tumours. The findings suggest that oligoclonal tumour development occurs in post-Chernobyl PTCs. This pattern of different clones within the tumour appears to become more discrete in cases with longer latencies, suggesting either outgrowth of individual clones or development of later subclones with time.

Gain of chromosome band 7q11 in papillary thyroid carcinomas of young patients is associated with exposure to low-dose irradiation

“…These findings indicate that the CNAs correlate with the morphological and molecular phenotypes of the investigated cases. The various copy number changes that are present in addition to the RET/PTC rearrangement in RET/PTC positive cases concur with the findings of previous studies reporting that RET/PTC only occurs in a subset of tumor cells and therefore is unlikely to be the only driver of PTCs (12,13,26). Many of the CNAs described in this study have already been described in PTCs from children in one of our previous studies (17) ( Table S5).…”

“…These findings may therefore reflect more the association between the solid morphological subtype with RET/PTC3 rearrangement and the age of the patient at diagnosis, rather than the etiology of the tumor (5, 10). In addition, the level of RET/PTC expression in PTC has been shown to be highly variable as a result of heterogeneous distribution of RET/PTC within a particular tumor (11)(12)(13)(14). This suggests that rearrangement of the RET oncogene may not be an initiating event and, therefore, the presence of a high frequency of this alteration is not directly linked to radiation exposure.…”

Role of H2O2 in RET/PTC1 Chromosomal Rearrangement Produced by Ionizing Radiation in Human Thyroid Cells

“…External radiation during childhood increases the risk of thyroid tumors, either benign or malignant (1)(2)(3)(4)8). More than 90% of these cancers are papillary, presenting a RET/ PTC rearrangement in 70% of cases.…”

Five Top Stories in Cytopathology

“…The translocations of RET and TRK are mostly intrachromosomal, 117 making them relatively difficult to detect by FISH. Studies using FISH to detect RET translocations have found alternating positive and negative areas within morphologically malignant cells of papillary thyroid carcinoma 118 -a finding that may reflect insensitivity of the FISH technique rather than the implausible alternative of multiple independent RET translocations. Polymerase chain reaction-based detection of the translocations is also difficult because the translocations can take place over a large distance.…”