INTRODUCTION Papillary thyroid carcinoma (PTC) originates from follicular cells of thyroid gland and it represents the most common type of thyroid cancer. About 10-20% of PTC cases harbor a RET/PTC rearrangement and the presence of these rearrangements is strongly associated to exposure to ionizing radiations and younger age. METHODS/CASE PRESENTATION In this study, we present the case of a 4 years old patient affected by classic variant PTC with lymph-node metastasis. After surgery, RNA and DNA were extracted from the primary tumor and 2 metastatic lymph-nodes. The cDNA was examined for the presence of RET/PTC 1 and 3 rearrangements by multiplex RT-PCR; amplicons obtained were then sequenced by Sanger method. The method of chromosome walking in the intronic regions of the genomic DNA of tumoral tissues was used to identify the breakpoint sites. RESULTS/DISCUSSION The results obtained on the primary tumor and metastatic tissues demonstrated the absence of a RET/PTC1 rearrangement but the presence of a RET/PTC3 rearrangement resulting in a shorter band length when compared to the positive control (300bp vs 430bp). Direct sequencing of the band obtained revealed a fusion between NCOA4 exon 6 and RET exon 12 with a skip of exon 7 of NCOA4 that is characteristic of the classic RET/PTC3 rearrangement. In order to further characterize the fusion on genomic DNA, we performed PCR with different primers located within intron 6-7 of NCOA4 and intron 11-12 of RET and the data obtained reveled a breakpoint within exon 11-12 of RET and within exon 7 of NCOA4, lost in the transcript after the splicing process. The patient’s personal and medical history did not show any link to radiation exposure or to other disruptors. Currently, a screening for this type of rearrangement on pediatric PTC patients with no history of radio exposure, is ongoing and chromosome fragility induced by other causes than radiation exposure are taken into consideration. CONCLUSIONS In conclusion, in this study we described an alternative and new RET/PTC3 rearrangement in a pediatric PTC patient. Apparently, the occurrence of this rearrangement is not linked to radiation exposure and other mechanisms are still under investigation.
A novel fusion RET/PTC3 involving NCOA4 and RET genes in a pediatric case of Papillary Thyroid Carcinoma
CIAMPI, RAFFAELE;ROMEI, CRISTINA;TACITO, ALESSIA;CASELLA, FRANCESCA;MOLINARO, ELEONORA;AGATE, LAURA;BOTTICI, VALERIA;MATRONE, ANTONIO;VITTI, PAOLO;ELISEI, ROSSELLA
2015-01-01
Abstract
INTRODUCTION Papillary thyroid carcinoma (PTC) originates from follicular cells of thyroid gland and it represents the most common type of thyroid cancer. About 10-20% of PTC cases harbor a RET/PTC rearrangement and the presence of these rearrangements is strongly associated to exposure to ionizing radiations and younger age. METHODS/CASE PRESENTATION In this study, we present the case of a 4 years old patient affected by classic variant PTC with lymph-node metastasis. After surgery, RNA and DNA were extracted from the primary tumor and 2 metastatic lymph-nodes. The cDNA was examined for the presence of RET/PTC 1 and 3 rearrangements by multiplex RT-PCR; amplicons obtained were then sequenced by Sanger method. The method of chromosome walking in the intronic regions of the genomic DNA of tumoral tissues was used to identify the breakpoint sites. RESULTS/DISCUSSION The results obtained on the primary tumor and metastatic tissues demonstrated the absence of a RET/PTC1 rearrangement but the presence of a RET/PTC3 rearrangement resulting in a shorter band length when compared to the positive control (300bp vs 430bp). Direct sequencing of the band obtained revealed a fusion between NCOA4 exon 6 and RET exon 12 with a skip of exon 7 of NCOA4 that is characteristic of the classic RET/PTC3 rearrangement. In order to further characterize the fusion on genomic DNA, we performed PCR with different primers located within intron 6-7 of NCOA4 and intron 11-12 of RET and the data obtained reveled a breakpoint within exon 11-12 of RET and within exon 7 of NCOA4, lost in the transcript after the splicing process. The patient’s personal and medical history did not show any link to radiation exposure or to other disruptors. Currently, a screening for this type of rearrangement on pediatric PTC patients with no history of radio exposure, is ongoing and chromosome fragility induced by other causes than radiation exposure are taken into consideration. CONCLUSIONS In conclusion, in this study we described an alternative and new RET/PTC3 rearrangement in a pediatric PTC patient. Apparently, the occurrence of this rearrangement is not linked to radiation exposure and other mechanisms are still under investigation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
