scholarly journals Targetable gene fusions identified in radioactive iodine refractory advanced thyroid carcinoma

2019 ◽  
Vol 180 (4) ◽  
pp. 235-241 ◽  
Author(s):  
K van der Tuin ◽  
M Ventayol Garcia ◽  
W E Corver ◽  
M N Khalifa ◽  
D Ruano Neto ◽  
...  

ObjectiveGene alterations leading to activation of the MAPK pathway are of interest for targeted therapy in patients with advanced radioactive iodine refractory (RAI-R) thyroid carcinoma. Due to technical reasons gene fusion analysis in RNA isolated from formalin-fixed tumor tissues has till now been limited. The objective of the present study was to identify targetable gene rearrangements in RNA isolated from formalin-fixed RAI-R thyroid carcinomas.DesignRetrospective study in 132 patients with RAI-R thyroid carcinoma (59 papillary-, 24 follicular-, 35 Hürthle cell- and 14 anaplastic thyroid carcinoma).MethodsTotal nucleic acid (undivided DNA and RNA) was isolated from formalin-fixed tissue. Extensive gene fusion analysis was performed in all samples that tested negative for pathogenicBRAF,NRAS,HRASandKRASvariants.ResultsSeven targetable gene fusions were identified in the remaining 60 samples without known DNA variants. This includes frequently reported gene fusions such asCCDC6/RET(PTC1),PRKAR1A/RET(PTC2) andETV6/NTRK3, and gene fusions that are less common in thyroid cancer (TPM3/NTRK1,EML4/ALKandEML4/NTRK3). Of note, most gene fusions were detected in papillary thyroid carcinoma and MAPK-associated alterations in Hürthle cell carcinomas are rare (2/35).ConclusionTargetable gene fusions were found in 12% of RAI-R thyroid carcinoma without DNA variants and can be effectively identified in formalin-fixed tissue. These gene fusions might provide a preclinical rationale to include specific kinase inhibitors in the treatment regimen for these patients. The latter intends to restore iodine transport and/or take advantage of the direct effect on tumor cell vitality once progressive disease is seen.

2018 ◽  
Author(s):  
Jeffrey Falk ◽  
Parth Sitlani ◽  
Claire Orosco ◽  
Maya Panjikaran ◽  
Dana Weiner ◽  
...  

2002 ◽  
Vol 166 (7) ◽  
pp. 994-997 ◽  
Author(s):  
Hajime Fukunaga ◽  
Tomoyuki Murakami ◽  
Toshikazu Gondo ◽  
Kazuo Sugi ◽  
Tokuhiro Ishihara

2011 ◽  
Vol 135 (1-2) ◽  
pp. 165-172 ◽  
Author(s):  
Bertrand Canard ◽  
Hortense Vachon ◽  
Thomas Fontaine ◽  
Jean-Jacques Pin ◽  
Stéphane Paul ◽  
...  

1999 ◽  
Vol 27 (16) ◽  
pp. i-iii ◽  
Author(s):  
N. J. Coombs ◽  
A. C. Gough ◽  
J. N. Primrose

1994 ◽  
Vol 42 (8) ◽  
pp. 1127-1134 ◽  
Author(s):  
J H Beckstead

Immunohistochemistry is a powerful tool for tissue diagnosis and research. Although the frozen section has remained the gold standard for this important approach to evaluation of antigens in tissues, there is widespread acknowledgment of many limitations. Routine paraffin-embedded sections ware widely used for morphological examination of tissues but are not optimal for antigen preservation. In this study, paraffin-embedded tissues fixed with a simple buffer containing zinc as the primary fixative were compared with tissues fixed with routine formalin, zinc-formalin, paraformaldehyde, ethanol, a variety of commercial (non-formalin-containing) fixatives that have been recommended for reduced toxicity and improved antigen survival, and frozen sections. Human lymphoid tissues and a group of antibodies to antigens (CD1, CD4, CD7, CD8, CD19) usually preserved only in frozen tissue were used as a model system. Fixation in a simple solution of zinc acetate and zinc chloride in a Tris-Ca acetate buffer resulted in antigen preservation comparable to that in frozen sections with antibodies to these cell surface markers. Morphological preservation was comparable to formalin-fixed sections. The work presents a new method that represents the closest approach yet to a technique that combines optimal antigenic survival with the convenience and morphological preservation of traditional formalin-fixed tissue embedded in paraffin.


2020 ◽  
Vol 29 (2) ◽  
pp. 165-174
Author(s):  
Nahid Parvez ◽  
Mustak Ibn Ayub

The necessary modifications in the protocol of general purpose DNA isolation kit to isolate and amplify a target region of genome from colorectal cancer tissues fixed in liquid formalin were made. It is shown that a one hour digestion with proteinase K yields enough DNA from formalin fixed colorectal tissue for subsequent PCR and sequencing. Moreover, using 100% ethanol instead of standard 50% during DNA binding step in the column improves the yield. As DNA fragmentation is unavoidable in formalin fixed tissue, PCR protocol was modified by increasing polymerase concentration to get successful amplification. Following these modifications, two regions of KRAS and BRAF genes were amplified and successfully sequenced from three different patients. These modifications provide a low cost option for Sanger sequencing of DNA isolated from formalin fixed tissue. Dhaka Univ. J. Biol. Sci. 29(2): 165-174, 2020 (July)


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