Prognostic impact of tumor mutation burden and the mutation in KIAA1211 in small cell lung cancer.

Zhou M1, Fan J2, Li Z1, Li P1, Sun Y1, Yang Y1, Zhou X1, Wang J1, Wang Y1, Qi H3, Cai W3, Dai X4, Hirsch FR5.

Author information

1: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, People's Republic of China.
2: Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
3: Shanghai Tongshu Biotechnology Co., Ltd, Shanghai, 200120, People's Republic of China.
4: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, People's Republic of China. 2003xh1047@hust.edu.cn.
5: Center for Thoracic Oncology, Tisch Cancer Center Mount Sinai Health System; Icahn School of Medicine at Mount Sinai, New York, USA. Fred.Hirsch@mssm.edu.

Abstract

BACKGROUND:

Small cell lung cancer (SCLC) is a highly aggressive lung cancer subtype with poor survival and limited treatment options. Sequencing results have revealed gene mutations associated with SCLC, however, the correlation between the genomic alterations and clinical prognosis of SCLC is yet unclear.

METHODS:

Targeted next-generation sequencing of 62 cancer related genes was performed on 53 SCLC samples. The correlations between clinical outcomes and genomic alterations were analyzed.

RESULTS:

38/62 (61.3%) candidate genes harbored some alterations, while all the SCLC samples carried at least 3 gene mutations. The most common nonsynonymous mutations included ERBB2 (95.9%), CREBBP (95.9%), and TP53 (77.6%). The median nonsynonymous tumor mutation burden (TMB) was 21.7 mutations/Mb (rang, 9.3-55.9). High TMB (> 21 mutations/Mb) was good prognostic factor in overall survival (OS) (21.7 vs. 10.4 months, P = 0.012). Multivariate analysis showed that high TMB was an independent prognostic factor. The overall survival (OS) of patients carrying KIAA1211 mutation was significantly longer than those with wild-type KIAA1211 (P < 0.001).

CONCLUSIONS:

The current study highlights the potential role of genomic alterations for the prognosis of SCLC. Higher TMB was associated with a better prognosis, and KIAA1211 might be a good prognostic factor in SCLC.