The purpose of this work was to investigate the distinct and common metabolic features of the malignant and benign thyroid lesions in reference to the non-transformed tissue from the contralateral gland (chronic thyroiditis and colloid goiter). 1H HR MAS NMR spectra of 38 malignant lesions, 32 benign lesions and 112 samples from the non-tumoral tissue (32 from chronic thyroiditis and 80 samples from colloid goiter) were subjected both to multivariate and univariate analysis. The increased succinate, glutamine, glutathione, serine/cysteine, ascorbate, lactate, taurine, threonine, glycine, phosphocholine/glycerophosphocholine and decreased lipids were found in both lesion types in comparison to either colloid goiter or chronic thyroiditis. The elevated glutamate and choline, and reduced citrate and glucose were additionally evident in these lesions in reference to goiter, while the increased myo-inositol—in comparison to thyroiditis. The malignant lesions were characterized by the higher alanine and lysine levels than colloid goiter and thyroiditis, while scyllo-inositol was uniquely increased in the benign lesions (not in cancer) in comparison to both non-tumoral tissue types. Moreover, the benign lesions presented with the unique increase of choline in reference to thyroiditis (not observed in the cancerous tissue). The metabolic heterogeneity of the non-tumoral tissue should be considered in the analysis of metabolic reprogramming in the thyroid lesions.
Thyroid nodules are frequently observed, particularly in individuals of over 60 years of age.On the other hand, most of the detected changes are benign and they do not require surgery. Therefore, differentiation between benign and malignant lesions in preoperative diagnosis is of crucial importance.Currently, the use of fine-needle aspiration biopsy (FNAB) and cytological assessment are the gold standard in the diagnosis of thyroid nodules. This procedure significantly reduces the need for diagnostic surgical intervention. However, approximately 15-30% of cytological results are classified as indeterminate. This is mainly due to the lack of specific cytomorphologic features that would facilitate the diagnosis based on cell evaluation under microscopic assessment. For the diagnoses of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), the assessment of invasion is crucial. Such an evaluation is not possible in cytology. Recently, molecular tests have been developed. They improve cytological diagnosis, particularly in the case of indeterminate results. Commercially available tests are developed based on the North American population. It is important to assess whether such tests can be used in the evaluation of e.g., European population.
Papillary thyroid carcinoma (PTC) is most common among all thyroid cancers. Multiple genomic alterations occur in PTC, and gene rearrangements are one of them. Here we screened 14 tumors for novel fusion transcripts by RNA‐Seq. Two samples harboring
RET/PTC1
and
RET/PTC3
rearrangements were positive controls whereas the remaining ones were negative regarding the common PTC alterations. We used Sanger sequencing to validate potential fusions. We detected 2 novel potentially oncogenic transcript fusions:
TG‐FGFR1
and
TRIM33‐NTRK1
. We detected 4 novel fusion transcripts of unknown significance accompanying the
TRIM33‐NTRK1
fusion:
ZSWIM5‐TP53BP2
,
TAF4B‐WDR1
,
ABI2‐MTA3
, and
ARID1B‐PSMA1
. Apart from confirming the presence of
RET/PTC1
and
RET/PTC3
in positive control samples, we also detected known oncogenic fusion transcripts in remaining samples:
TFG‐NTRK1
,
ETV6‐NTRK3
,
MKRN1‐BRAF
,
EML4‐ALK
, and novel isoform of
CCDC6‐RET
.
The exposure of leukemic blasts to drugs initiates a complex cellular response, which reflects global changes in gene expression. Changes in the expression of several genes are highly correlated with drug resistance.
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