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- 저자 : Yin Yu Pang (검색결과 2 건)
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Yuchun Wei,Chuqing Wei,Liang Chen,Ning Liu,Qiuxiang Ou,Jiani C. Yin,Jiaohui Pang,Zhenhao Fang,Xue Wu,Xiaonan Wang,Dianbin Mu,Yang Shao,Jinming Yu,Shuanghu Yuan 대한암학회 2022 Cancer Research and Treatment Vol.54 No.4
Purpose Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence. PurposeNeoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer.Materials and MethodsA total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits.ResultsGenetic alterations of <i>PIK3CA</i> were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including <i>TERT, POLD1, NOS2</i>, and <i>FGFR3</i> was significantly higher in Chinese patients whereas <i>RPTOR, EGFR</i>, and <i>TP53</i> were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including <i>BRCA1/2, TP53</i> and <i>PALB2</i>. Importantly, high tumor mutation burden, <i>TP53</i> polymorphism (rs1042522), and <i>KEAP1</i> mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. <i>KEAP1</i> mutations, <i>PIK3CA-SOX2</i> co-amplification, <i>TERC</i> copy number gain, and <i>TYMS</i> polymorphism correlated with an increased risk of disease relapse.ConclusionWe report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.
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