HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma

Ciampi, Raffaele; Giordano, Thomas J.; Wikenheiser-Brokamp, Kathryn A.; Koenig, Ronald J.; Nikiforov, Yuri E.

doi:10.1677/erc-07-0039

Cited by 71 publications

(40 citation statements)

References 30 publications

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“…RET/PTC2 and nine more recently identified types of RET/PTC are all interchromosomal translocations (reviewed in Ciampi et al 28 ). All rearrangement types contain the intact tyrosine kinase domain of the RET receptor and enables the RET/PTC chimeric protein to activate the RAS-RAF-MAPK cascade and initiate thyroid tumorigenesis.…”

Section: -27mentioning

confidence: 99%

Molecular analysis of thyroid tumors

2011

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Section: -27mentioning

confidence: 99%

Molecular analysis of thyroid tumors

2011

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“…No RET/PTC1, -2 or -3 rearrangements were identified in PTC. However, as other rearrangements involving the RET (Ciampi et al, 2007) or NTRK1 (Pierotti and Greco, 2006) genes have also been described in PTC, we specifically analysed RET and NTRK1 microarray mRNA expression in PTC negative for mutations. In one cPTC (sample 2 -Supplementary Table 1), a 20-fold increase in RET expression was detected in comparison to the other samples.…”

Section: Mutation Screeningmentioning

confidence: 99%

Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas

et al. 2009

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BACKGROUND: Poorly differentiated thyroid carcinomas (PDTC) represent a heterogeneous, aggressive entity, presenting features that suggest a progression from well-differentiated carcinomas. To elucidate the mechanisms underlying such progression and identify novel therapeutic targets, we assessed the genome-wide expression in normal and tumour thyroid tissues. METHODS: Microarray analyses of 24 thyroid carcinomas -7 classic papillary, 8 follicular variants of papillary (fvPTC), 4 follicular (FTC) and 5 PDTC -were performed and correlated with RAS, BRAF, RET/PTC and PAX8-PPARG alterations. Selected genes were validated by quantitative RT -PCR in an independent set of 28 thyroid tumours. RESULTS: Unsupervised analyses showed that gene expression similarity was higher between PDTC and fvPTC, particularly for tumours harbouring RAS mutations. Poorly differentiated thyroid carcinomas presented molecular signatures related to cell proliferation, poor prognosis, spindle assembly checkpoint and cell adhesion. Compared with normal tissues, PTC had 307 out of 494 (60%) genes over-expressed, FTC had 137 out of 171 (80%) genes under-expressed, whereas PDTC had 92 out of 107 (86%) genes under-expressed, suggesting that gene downregulation is involved in tumour dedifferentiation. Significant UHRF1 and ITIH5 deregulated gene expression in PDTC, relatively to normal tissues, was confirmed by quantitative RT -PCR. CONCLUSION: Our findings suggest that fvPTC are possible precursors of PDTC. Furthermore, UHRF1 and ITIH5 have a potential therapeutic/prognostic value for aggressive thyroid tumours.

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“…In PTC, the RET proto-oncogene is activated by fusion of the RET TK domain with the 5 ¶ terminal sequence of one of different heterologous genes via rearrangements that generate a series of chimeric-transforming oncogenes collectively described as RET/PTCs. To date, at least 12 rearranged forms of the RET gene have been isolated, of which RET/PTC1 and RET/PTC3 are by far the most common (12). RET/PTC rearrangements were commonly found in childhood PTC regardless of radiation history (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

RET/PTC Rearrangements Preferentially Occurred in Papillary Thyroid Cancer among Atomic Bomb Survivors Exposed to High Radiation Dose

Hamatani¹,

Eguchi

Ito³

et al. 2008

Cancer Research

145

114

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A major early event in papillary thyroid carcinogenesis is constitutive activation of the mitogen-activated protein kinase signaling pathway caused by alterations of a single gene, typically rearrangements of the RET and NTRK1 genes or point mutations in the BRAF and RAS genes. In childhood papillary thyroid cancer, regardless of history of radiation exposure, RET/PTC rearrangements are a major event. Conversely, in adult-onset papillary thyroid cancer among the general population, the most common molecular event is BRAF V600E point mutation, not RET/PTC rearrangements. To clarify which gene alteration, chromosome aberration, or point mutation preferentially occurs in radiation-associated adultonset papillary thyroid cancer, we have performed molecular analyses on RET/PTC rearrangements and BRAF V600E mutation in 71 papillary thyroid cancer cases among atomic bomb survivors (including 21 cases not exposed to atomic bomb radiation), in relation to radiation dose as well as time elapsed since atomic bomb radiation exposure. RET/PTC rearrangements showed significantly increased frequency with increased radiation dose (P trend = 0.002). In contrast, BRAF V600E mutation was less frequent in cases exposed to higher radiation dose (P trend < 0.001). Papillary thyroid cancer subjects harboring RET/PTC rearrangements developed this cancer earlier than did cases with BRAF V600E mutation (P = 0.03). These findings were confirmed by multivariate logistic regression analysis. These results suggest that RET/PTC rearrangements play an important role in radiation-associated thyroid carcinogenesis.

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HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma

Cited by 71 publications

References 30 publications

Molecular analysis of thyroid tumors

Molecular analysis of thyroid tumors

Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas

RET/PTC Rearrangements Preferentially Occurred in Papillary Thyroid Cancer among Atomic Bomb Survivors Exposed to High Radiation Dose

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