{'fraction_non_alphanumeric': 0.04198473282442748, 'fraction_numerical': 0.023377862595419848, 'mean_word_length': 5.008595988538682, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Mutational landscape of homologous recombination-related genes in small-cell lung cancer.

BACKGROUND
Homologous recombination deficiency (HRD) is a well-known biomarker which could predict poly-ADP ribose polymerase 1 (PARP) inhibitor and platinum drug response. As an aggressive cancer, small-cell lung cancer (SCLC) is sensitive to platinum drugs, but relapse occurs rapidly. Herein, we aim to illustrate the genomic alteration patterns of homologous recombination repair (HRR)-related genes in a Chinese SCLC cohort and further analyze the relationship among HRR gene mutations and known biomarkers of immune checkpoint inhibitor (ICI) response, including tumor mutation burden (TMB) and programmed cell death-ligand 1 (PD-L1) expression.


METHODS
Next-generation sequencing (NGS)-based target capture sequencing of 543 cancer-related genes was performed to analyze the genomic profiles of 133 Chinese SCLC patients, and TMB was calculated. PD-L1 expression was evaluated in 90 out of 133 patients using the SP142 PD-L1 immunohistochemistry assay.


RESULTS
Among the 133 patients with SCLC, 47 (35.3%) had HRR gene mutations. ATM (8.3%) was the most frequently mutated HRR gene in the cohort, followed by NBN (4.5%). Pathogenic somatic and germline mutations of HRR genes were identified in 11 (23.4%) and 4 (8.5%) patients, respectively. HRR gene mutations cooccurred with KMT2D gene mutations. There were several differences in genomic alterations between patients with HRR gene mutations (HRR-Mut) and without HRR mutations (HRR-WT). The results revealed that TP53 and RB1 were commonly mutated genes in both groups. Mutations in the KMT2D gene and genes in the RTK-RAS pathway occurred more frequently in the HRR-Mut group. Furthermore, we found that mutations in HRR genes were associated with high TMB (Wilcoxon, p = 0.048), but there was no correlation of HRR gene mutation status with PD-L1 expression.


CONCLUSIONS
We exhaustively describe the genomic alteration profile of Chinese SCLC patients and provide further evidence that HRR gene mutations are prevalent in SCLC patients.