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An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
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Distinct ALK Expression Patterns Are Associated with Canonical and Noncanonical STRN::ALK Transcript Architectures in

Debora Mota Dias Thomaz1, Thais Biude Mendes1, Thaise Nayane Ribeiro Carneiro1,2

  • 1Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo - Escola Paulista de Medicina, Pedro de Toledo 669, 11th floor, São Paulo, SP, 04039-032, Brazil.

Endocrine Pathology
|July 2, 2026
PubMed

Insights

STRN::ALK fusions in oncocytic thyroid neoplasms show diverse structures. Only canonical fusions yield detectable ALK protein, impacting therapeutic relevance for these rare thyroid cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oncocytic thyroid carcinomas present unique chromosomal features and resistance to radioactive iodine therapy.
  • The role of ALK rearrangements, specifically STRN::ALK fusions, in oncocytic thyroid neoplasms requires further investigation due to unclear biological and clinical significance.

Purpose of the Study:

  • To investigate the frequency and characteristics of STRN exon 3-ALK exon 20-derived transcripts in oncocytic thyroid neoplasms.
  • To evaluate the biological and clinical implications of different STRN::ALK transcript architectures, including ALK protein expression and potential therapeutic relevance.

Main Methods:

  • RT-PCR was used to detect STRN::ALK transcripts in 56 oncocytic thyroid neoplasms.
  • Positive cases underwent cloning, Sanger sequencing, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and in silico structural modeling.

Main Results:

  • STRN::ALK transcripts were found in 9 of 56 tumors, with 2 (3.6%) canonical in-frame fusions and 7 (12.5%) noncanonical out-of-frame variants.
  • ALK rearrangement by FISH was confirmed in all transcript-positive cases, but detectable ALK protein by IHC was only seen in canonical fusions.
  • Structural modeling suggested preserved kinase-domain function in canonical fusions and disruption in noncanonical variants.

Conclusions:

  • STRN::ALK transcripts in oncocytic thyroid neoplasms display significant architectural heterogeneity.
  • ALK FISH-positive/IHC-negative cases require cautious interpretation due to potential lack of biological equivalence and uncertain therapeutic relevance.
  • Integrated molecular and protein-level analysis is crucial for accurate interpretation of ALK alterations in these neoplasms.
Keywords:
ALK Fusion ProteinsAnaplastic Lymphoma KinaseFluorescence In Situ Hybridization.ImmunohistochemistryOncocytic Thyroid Neoplasms

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