Ren Min, Zhang Jing, Kong Yunyi, Bai Qianming, Qi Peng, Zhang Ling, Wang Qian, Zhou Xiaoyan, Chen Yong, Zhu Xiaoli
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Ann Transl Med. 2022 Jan;10(2):31. doi: 10.21037/atm-21-4235.
Discrepancies in genetic alterations found in melanoma are conspicuous between different ethnic groups. With the approval of BRAF- and MEK-targeted inhibitors in China, it is necessary to further elucidate the landscape of gene mutation in Chinese melanoma patients.
The frequency and distribution of , , and mutations in 691 melanoma patients was determined, and the statistical significance of correlations between different gene mutations and clinicopathological features was analyzed.
Among a total of 691 patients, mutation was found in 166 patients (24.0%), and V600E was the prominent genetic alteration (145/166, 87.3%). Statistical analyses showed that younger patients (<60) had a higher mutation rate than older patients (≥60, P=0.000), and the frequency of mutation was more likely to be lower in patients with the following: melanoma located in an extremity (P=0.000), acral-lentiginous melanoma subtype (P=0.000), thinner melanoma thickness (P=0.047), and no ulceration (P=0.030). The frequency of mutation was 12.6% (38/302), and primarily involved codon 61 in exon 3 and codon 12 in exon 2. Mutation of was detected in 65 patients (9.4%), and the most common site of mutations was L576 in exon 11 (29/65, 44.6%). Patients with or mutation had higher Clark level (P=0.035 and 0.047, respectively) and were more likely to have melanoma located in an extremity (P=0.003 and 0.009, respectively) than those without such mutation. The concordance of gene mutations between paired primary and metastatic lesions was 89.6% (60/67), and visceral metastases showed the highest distribution of gene mutations versus primary melanomas (100.0%) compared with lymph nodes (90.9%) and cutaneous metastases (83.3%).
In this large cohort of Chinese melanoma patients, the frequencies of and mutations were lower than those observed in Caucasian cohorts, but the clinicopathological features of , , and mutation were consistent. Paired primary and metastatic lesions showed high concordance of gene mutations.
黑色素瘤中发现的基因改变在不同种族群体之间存在显著差异。随着BRAF和MEK靶向抑制剂在中国获批，有必要进一步阐明中国黑色素瘤患者的基因突变情况。
测定691例黑色素瘤患者中 、 和 突变的频率及分布，并分析不同基因突变与临床病理特征之间相关性的统计学意义。
在总共691例患者中，166例患者（24.0%）检测到 突变，其中V600E是主要的基因改变（145/166，87.3%）。统计分析表明，年轻患者（<60岁）的 突变率高于老年患者（≥60岁，P=0.000），并且在以下患者中 突变频率更可能较低：位于四肢的黑色素瘤（P=0.000）、肢端雀斑样痣黑色素瘤亚型（P=0.000）、黑色素瘤厚度较薄（P=0.047）以及无溃疡（P=0.030）。 突变频率为12.6%（38/302），主要涉及外显子3中的第61密码子和外显子2中的第12密码子。65例患者（9.4%）检测到 突变，最常见的突变位点是外显子11中的L576（29/65，44.6%）。与没有这些突变的患者相比，有 或 突变的患者具有更高的Clark分级（分别为P=0.035和0.047），并且更可能患有位于四肢的黑色素瘤（分别为P=0.003和0.009）。配对的原发性和转移性病变之间基因突变的一致性为89.6%（60/67），与淋巴结（90.9%）和皮肤转移灶（83.3%）相比，内脏转移灶的基因突变分布与原发性黑色素瘤相比最高（100.0%）。
在这一大型中国黑色素瘤患者队列中， 和 突变频率低于白种人队列中观察到的频率，但 、 和 突变的临床病理特征是一致的。配对的原发性和转移性病变显示出较高的基因突变一致性。
