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KRAS 和 BRAF 突变与鼻腔鼻窦癌。

KRAS and BRAF mutations in sinonasal cancer.

机构信息

Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Spain.

出版信息

Oral Oncol. 2012 Aug;48(8):692-7. doi: 10.1016/j.oraloncology.2012.02.018. Epub 2012 Mar 27.

Abstract

OBJECTIVES

[corrected] Despite improvements in the field of surgery and radiotherapy, the overall prognosis of sinonasal carcinomas is poor, mainly due to the difficulty to resect the tumour completely in this anatomically complex region. Therefore, there is great need for alternative treatments. Knowledge of the KRAS and BRAF mutational status would become clinically important with regard to the possible use of anti-EGFR therapies.

MATERIAL AND METHODS

DNA was extracted from paraffin embedded tumour samples from 57 cases of sinonasal squamous cell carcinoma (SNSCC) and from fresh frozen tumour samples from 58 cases of intestinal-type sinonasal adenocarcinoma (ITAC). Point mutations were analysed for KRAS exon 2 (codons 12 and 13) and BRAF (exon 15, V600E) by direct sequencing.

RESULTS

Neither KRAS nor BRAF showed any mutations in the SNSCC, whereas 7/58 (12%) ITAC harboured KRAS mutations and no BRAF mutations. All seven cases with KRAS mutation concerned well-differentiated and less aggressive (papillary and colonic type) ITAC, all patients being woodworkers and 4/7 tobacco smokers.

CONCLUSION

Neither of SNSCCs carried mutations in KRAS and BRAF and a low frequency of KRAS mutation was found in ITAC. This suggests that KRAS and BRAF mutations play a limited role in the development of sinonasal cancer and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in sinonasal cancer.

摘要

目的

尽管在外科手术和放射治疗领域取得了进展,但鼻窦癌的总体预后仍然较差,主要是因为在这个解剖结构复杂的区域很难完全切除肿瘤。因此,需要寻找替代治疗方法。了解 KRAS 和 BRAF 突变状态对于可能使用抗 EGFR 治疗将具有重要的临床意义。

材料和方法

从 57 例鼻窦鳞状细胞癌(SNSCC)的石蜡包埋肿瘤样本和 58 例肠型鼻窦腺癌(ITAC)的新鲜冷冻肿瘤样本中提取 DNA。通过直接测序分析 KRAS 外显子 2(密码子 12 和 13)和 BRAF(外显子 15,V600E)的点突变。

结果

SNSCC 中既没有 KRAS 也没有 BRAF 突变,而 58 例 ITAC 中有 7/58(12%)存在 KRAS 突变,没有 BRAF 突变。所有 7 例 KRAS 突变均涉及分化良好且侵袭性较低的(乳头状和结肠型)ITAC,所有患者均为木工,4/7 为吸烟者。

结论

SNSCC 中均未携带 KRAS 和 BRAF 突变,而 ITAC 中 KRAS 突变的频率较低。这表明 KRAS 和 BRAF 突变在鼻窦癌的发生发展中作用有限,突变分析作为鼻窦癌对抗 EGFR 治疗敏感性的筛选试验并不有用。

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