Correlation between mutation spectrum and clinicopathological characteristics of Chinese patients with thyroid cancer

Not long ago, Dr.
Wang Zhuo’s team from Jiangsu Cancer Hospital used next-generation sequencing (NGS) technology to analyze mutation profiles, providing new insights for a comprehensive understanding of TC biology
.

Through NGS, 225 formalin-fixed and paraffin-embedded surgically resected thyroid tissue specimens were sequenced to detect 15 target genes.
The authors analyzed the mutation spectrum and clinicopathological characteristics of Chinese patients with thyroid cancer (TC) The relationship between
.

The study detected 207 mutations, including 200 mutations in 81.
40% papillary thyroid cancer samples, 3 mutations in 50.
00% medullary thyroid cancer samples, and 4 mutations in 100% anaplastic thyroid cancer samples
.

19.
56% of samples had no target gene mutations, 69.
78% of samples contained single gene mutations, 9.
78% of samples had two gene mutations, and 0.
89% of samples had triple different gene mutations
.

For PTC, BRAF mutation predominates, TERT mutation is more common in advanced PTC, and RET fusion is only observed in PTC
.

For MTC, RET point mutations dominate
.

For samples that carry more than one genetic mutation, the allele frequencies of the mutants are almost similar
.

Among patients 55 years and older (p <.
001) and American Joint Committee on Cancer (AJCC) advanced cancer staging (p <.
001), multiple mutations in TC patients are significantly more frequent
.

Gender (p = .
309) and pathological subtype (p = .
121) did not show a significant correlation with mutations
.

The analysis between mutation profiles and clinicopathological features provides new insights into the biology of TC, and is expected to improve the accuracy of TC diagnosis and prognosis, thereby promoting precise treatment of TC patients
.

Thyroid cancer (TC) is the most common endocrine tumor
.

In recent decades, its incidence has been on the rise
.

According to the clinical practice guidelines of the National Comprehensive Cancer Network, thyroid cancer is divided into four types: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC) and undifferentiated thyroid carcinoma (ATC)
.

Previous results indicate that BRAF, NRAS, KRAS, HRAS, TERT, RET, PIK3CA, PTEN, TP53, AKT1, GNAS, CTNNB1, PAX8/PPARã, TSHR somatic mutations and NTRK1 gene are related to the diagnosis and treatment of TC
.

Therefore, molecular detection of these 15 target genes will help to develop individualized treatment strategies for TC
.

Next-generation sequencing (NGS) is a newly developed technology that can simultaneously detect multiple genetic variants, and can efficiently and economically detect tumor mutations
.

In this study, the research team focused on NGS in the key exons of BRAF, NRAS, KRAS, HRAS, TERT, RET, PIK3CA, PTEN, TP53, AKT1, GNAS, CTNNB1, PAX8/PPARã, TSHR and NTRK genes.
The application of the primer pool composed of introns, and the analysis of the mutation spectrum and clinicopathological characteristics of Chinese TC patients
.

In the past, single-gene detection, especially BRAF point mutations, usually found molecular changes in TC through Sanger sequence, immunohistochemistry, and real-time PCR
.

In this study, the authors used NGS-based detection methods to simultaneously analyze multiple hotspot mutations in a single experiment
.

This method provides a valuable tool for a comprehensive understanding of the molecular events that have changed in TC
.

Due to the limitation of the sample size and the patient's coming from a specific geographic area, some mutations (such as AKT1, TSHR, KRAS, PETN and PAX8 mutations) in TC patients in this study were negative, which is different from previous studies
.

The analysis of this study shows that the molecular profiles of the four TC subtypes are different
.

The PTC samples are dominated by BRAF mutations, and the MTC samples are dominated by RET point mutations, which is consistent with previous studies
.

Published literature shows that RAS mutations (HRAS, KRAS, and NRAS) are common in FTC, while BRAF, PIK3CA, and PTEN mutations are common in ATC
.

In contrast, the different results of mutations in FTC samples and ATC samples in this study may be caused by insufficient sample size (1 FTC patient and 5 ATC patients)
.

TERT mutations have been shown to be associated with increased invasion and poor prognosis
.

Ke et al.
found no TERT mutation in PTC patients in their study
.

However, in two other studies conducted in China, TERT mutations were found in 4.
4% (20/455) and 4.
1% (27/653) of PTC patients, respectively
.

The analysis of this study showed that 7.
9% (17/215) of PTC patients had TERT mutations, and it was more common in patients with advanced PTC
.

In addition, Liu et al.
and Shi et al.
found TERT mutations in ATC patients were 46.
3% (25/54) ​​and 38.
7% (41/106), respectively
.

However, the authors did not find TERT mutations in ATC patients, and the different results may be caused by the small sample size of ATC
.

Regarding the occurrence of multiple mutations in TC, there have been reports before, and this situation has also been observed in this research analysis
.

For samples with multiple mutations, the allele frequencies of the mutations are similar, indicating that these mutations exist in the same clonal population of cells
.

But for samples containing NRAS, TERT, and TP53 mutations, the allele frequency of TP53 mutations was significantly lower than other samples
.

This finding may be due to the fact that TP53 mutation is a late event in tumor clonal progression
.

Cho et al.
found that high tumor mutation burden is related to the early stage of gastric cancer
.

In contrast, multiple mutations in TC patients in this study were significantly related to advanced AJCC cancer staging
.

In conclusion, the analysis between mutation profiles and clinicopathological features provides new insights into the biology of TC, and is expected to improve the accuracy of TC diagnosis and prognosis, thereby facilitating the precise treatment of TC patients
.

Link to the original text: https://doi.
org/10.
1002/prm2.
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