New Potential Targets Give Hope for Thyroid Cancer Treatment

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Whole-exome sequencing identified genetic mutations associated with poorly differentiated thyroid cancer, paving a new path for research in the field.

Thyroid cancer of a woman, medically 3D illustration, front view: © Axel Kock - stock.adobe.com

Thyroid cancer of a woman, medically 3D illustration, front view: © Axel Kock - stock.adobe.com

Findings from a cohort study have identified potential targetable genetic mutations and clinical pathology characteristics in poorly differentiated thyroid cancer (PDTC), opening the doors for new research into this difficult-to-treat cancer.1

Whole-exome sequencing was performed on 15 patients with PDTC at Gachon University Gil Medical Center, South Korea. RAS mutations, including HRAS, KRAS, and NRAS, were identified in 53.3% (n = 8) of patients, which is more frequent than the previously recorded incidence of 28%.

A RAS copy number gain or amplification was observed in 4 patients. The BRAF mutation, which has been previously reported as occurring in 33% of patients with PDTC, was not observed in any patients in this cohort.

“Compared [with differentiated thyroid carcinoma] such as papillary thyroid carcinoma, and follicular thyroid carcinoma [FTC], which differentiate well by pathological standards and have good prognosis, PDTC and anaplastic thyroid carcinoma have a relatively poor prognosis and a higher risk of metastasis or recurrence,” study authors wrote. “By providing molecular genetic insight on PDTC, this study may contribute to the discovery of novel therapeutic target candidates.”

Alterations in New Genes

Further, genomic alterations were observed in RAF1, MAP2K2, and AKT2, which have not been identified as potential targets in gene panel sequencing for PDTC. Regarding pathologic characteristics, 13 patients had a solid cell pattern, 5 patients had an insular pattern, and 9 patients had a trabecular pattern.

Investigators also identified certain genes that correlated with various cell patterns. The trabecular pattern was associated with ABCA12, CLIP1, and NRAS, while ABCA4 and SLIT3 were associated with the insular pattern. Moreover, a vascular invasion phenotype was related to ABCA12, ATP13A2, and CLIP1 genes, and INTS1 and RYR1 genes were related to capsular invasion.

“It is worth noting that our study stands out in terms of [whole-exome sequencing] analysis by utilizing data from 15 patients of PDTC originated from FTC, representing a relatively large sample size compared [with]previous PDTC [whole-exome sequencing] studies. This substantial dataset allowed us to draw robust conclusions and identify potential clinical implications,” study authors added.

Regarding patient characteristics, extrathyroidal extension was observed in 1 patient. Fourteen patients had capsule formation. Capsular invasion was identified in 10 patients, while vascular invasion was identified in 6 patients. None of the 15 patients had lymph node metastasis.

Study investigators used the SureSelect XT V6 Library Prep Kit as the exome library and Illumina as the sequencing platform.

A potential drawback of the study was its small sample size; study authors concluded that validation of the findings would be necessary through larger-scale cohort studies and multi-omics tumor profiling.

REFERENCE:
1. Lee Y, Moon S, Seok JY, et al. Characterization of the genomic alterations in poorly differentiated thyroid cancer. Sci Rep. 2023(13):19154.doi:10.1038/s41598-023-46466-5
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