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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2022.10
- 수록면
- 1,209 - 1,218 (10page)
- DOI
- 10.4143/crt.2021.963
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초록· 키워드
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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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