Huanli Duan1, Yan Li2, Peizhen Hu3, Jie Gao1, Jianming Ying2, Wanni Xu3, Danhui Zhao3, Zhe Wang3, Junyi Ye4, Analyn Lizaso4, Yangzhige He5, Huanwen Wu1, Zhiyong Liang1. 1. Department of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. 2. Department of Pathology, National Cancer Centre/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3. State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China. 4. Burning Rock Biotech, Guangzhou, China. 5. Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Abstract
AIMS: To characterise the mutational profiles of poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) and to identify markers with potential diagnostic, prognostic and therapeutic significance. METHODS AND RESULTS: Targeted next-generation sequencing with a panel of 18 thyroid carcinoma-related genes was performed on tissue samples from 41 PDTC and 25 ATC patients. Genetic alterations and their correlations with clinicopathological factors, including survival outcomes, were also analysed. Our results showed that ATC had significantly higher mutation rates of BRAF, TP53, TERT and PIK3CA than PDTC (P = 0.005, P = 0.007, P = 0.005, and P = 0.033, respectively). Nine (69%) ATC cases with papillary thyroid carcinoma (PTC) components harboured BRAF mutations, all of which coexisted with a late mutation event (TP53, TERT, or PIK3CA). Nine cases with oncogenic fusion (six RET cases, one NTRK1 case, one ALK case, and one PPARG case) were identified in 41 PDTCs, whereas only one case with oncogenic fusion (NTRK1) was found among 25 ATCs. Moreover, all six cases of RET fusion were found in PDTC with PTC components, accounting for 33%. In PDTC/ATC patients, concurrent TERT and PIK3CA mutations were associated with poor overall survival after adjustment for TNM stage (P = 0.001). CONCLUSIONS: ATC with PTC components is typically characterised by a BRAF mutation with a late mutation event, whereas PDTC with PTC components is more closely correlated with RET fusion. TERT and concurrent PIK3CA mutations predict worse overall survival in PDTC/ATC patients.
AIMS: To characterise the mutational profiles of poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) and to identify markers with potential diagnostic, prognostic and therapeutic significance. METHODS AND RESULTS: Targeted next-generation sequencing with a panel of 18 thyroid carcinoma-related genes was performed on tissue samples from 41 PDTC and 25 ATC patients. Genetic alterations and their correlations with clinicopathological factors, including survival outcomes, were also analysed. Our results showed that ATC had significantly higher mutation rates of BRAF, TP53, TERT and PIK3CA than PDTC (P = 0.005, P = 0.007, P = 0.005, and P = 0.033, respectively). Nine (69%) ATC cases with papillary thyroid carcinoma (PTC) components harboured BRAF mutations, all of which coexisted with a late mutation event (TP53, TERT, or PIK3CA). Nine cases with oncogenic fusion (six RET cases, one NTRK1 case, one ALK case, and one PPARG case) were identified in 41 PDTCs, whereas only one case with oncogenic fusion (NTRK1) was found among 25 ATCs. Moreover, all six cases of RET fusion were found in PDTC with PTC components, accounting for 33%. In PDTC/ATC patients, concurrent TERT and PIK3CA mutations were associated with poor overall survival after adjustment for TNM stage (P = 0.001). CONCLUSIONS: ATC with PTC components is typically characterised by a BRAF mutation with a late mutation event, whereas PDTC with PTC components is more closely correlated with RET fusion. TERT and concurrent PIK3CA mutations predict worse overall survival in PDTC/ATC patients.
Authors: Jae-Hui Kim; Ji Yun Jeong; An Na Seo; Nora Jee-Young Park; Moonsik Kim; Ji Young Park Journal: In Vivo Date: 2022 Jan-Feb Impact factor: 2.155
Authors: Bin Xu; Julia David; Snjezana Dogan; Iñigo Landa; Nora Katabi; Maelle Saliba; Anjanie Khimraj; Eric J Sherman; Robert Michael Tuttle; Giovanni Tallini; Ian Ganly; James A Fagin; Ronald A Ghossein Journal: Histopathology Date: 2021-10-07 Impact factor: 7.778