Clinical Features and Prognostic Significance of NOTCH1 Mutations in Diffuse Large B-Cell Lymphoma

Zhongqi Li; Fang Yu; Wenle Ye; Liping Mao; Jiansong Huang; Yang Shao; Junrong Yan; Wenjuan Yu; Jie Jin; Jinghan Wang

doi:10.3389/fonc.2021.746577

Clinical Features and Prognostic Significance of NOTCH1 Mutations in Diffuse Large B-Cell Lymphoma

Front Oncol. 2021 Dec 9:11:746577. doi: 10.3389/fonc.2021.746577. eCollection 2021.

Authors

Zhongqi Li¹, Fang Yu², Wenle Ye³, Liping Mao^{3

4

5

6}, Jiansong Huang^{3

4

5

6}, Yang Shao⁷, Junrong Yan⁷, Wenjuan Yu^{3

4

5

6}, Jie Jin^{3

4

5

6}, Jinghan Wang^{3

4

5

6}

Affiliations

¹ The Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
² Department of Pathology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.
³ Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China.
⁴ The First Affiliated Hospital of Zhejiang University, Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, China.
⁵ Institute of Hematology, Zhejiang University, Hangzhou, China.
⁶ Cancer Center, Zhejiang University, Hangzhou, China.
⁷ Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, China.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of large lymphoid B cell malignancy with distinct clinical and genetic features. Recently, NOTCH1 mutations were identified in DLBCL cases by Next-generation sequencing (NGS), but the clinical features and prognostic impact were not systematically studied. Here, NOTCH1 genes in 161 DLBCL samples were sequenced by NGS. The prognostic value of NOTCH1 mutations was assessed in the context of clinical and laboratory factors, such as international prognostic index (IPI), cell-of-origin classification, double expression of BCL2 and c-MYC. The combined data from three Western cohorts were used to validate these results. As a result, NOTCH1 mutations were found in 17(10.6%) patients, and three patients had a hotspot mutation of c.7541_7542delCT. The presence of NOTCH1 mutations was significantly associated with poor complete response and progression free survival(PFS), which was independent of established clinical and laboratory parameters. In addition, 30 (1.92%) of 1562 patients treated with R-CHOP regimen in those combined Western cohorts had NOTCH1 mutations. Meta-analysis of the Western cohorts confirmed that NOTCH1 mutations were also associated with poor PFS and OS. In conclusion, DLBCL patients with the NOTCH1 mutations have worse PFS and OS, and the NOTCH1 mutations can be used as an independent predictor for patients with DLBCL.

Keywords: NOTCH1 mutations; clinical decision making; clinical outcome; diffuse large B-cell lymphoma; next generation sequencing (NGS).