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Purpose:Patients with alveolar soft part sarcoma (ASPS) are rare and have few treatment options. We assessed the activity of geptanolimab (GB226), a fully humanized programmed cell death protein 1 antibody, for patients with unresectable, recurrent, or metastatic ASPS.Patients and Methods:We conducted this multicenter, single-arm, phase II study (Gxplore-005, NCT03623581) in patients aged 18–75 years who had unresectable, recurrent, or metastatic ASPS at 11 sites in China. Patients received intravenous geptanolimab (3 mg/kg) every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by independent review committee (IRC) per RECIST 1.1 in the full analysis set population.Results:Between September 6, 2018 and March 6, 2019, we enrolled and treated 37 patients with 23 (62.2%) having received prior systemic treatment. Fourteen [37.8%; 95% confidence interval (CI), 22.5–55.2] of 37 patients had an objective response assessed by IRC with a 6-month duration of response rate of 91.7%. Median progression-free survival was 6.9 months (95% CI, 5.0–not reached) and disease control was achieved in 32 (86.5%; 95% CI, 71.2–95.5) patients. Three of 37 patients reported grade 3 treatment-related adverse events (TRAEs), including anemia, hypophysitis, and proteinuria [one each (2.7%)]. No grade 4 TRAEs were observed. Two (5.4%) patients discontinued treatment due to TRAEs (one with hypophysitis and one with Mobitz type I atrioventricular block). The baseline percentage of CD4+ T cells was adversely associated with patient response (P = 0.031).Conclusions:Geptanolimab has clinically meaningful activity and a manageable safety profile in unresectable, recurrent, or metastatic ASPS.

supplementary data-tracking

Purpose: To investigate the association between lactate dehydrogenase (LDH) and the prognosis of first-line therapy in patients with small cell lung cancer (SCLC). Methods: 163 small cell lung cancer patients were consecutively included from January 2011 to June 2020 as initial therapy in Fujian Medical University Union Hospital. A retrospective analysis of the clinical data were conducted to explore the association between LDH, the progression free survival (PFS) and overall survival (OS). PFS and OS were calculated using the Kaplan-Meier method and compared with the log-rank test. Results: 163 patients were divided into 90 patients in the high LDH group (pre-treatment LDH≥202 IU/L) and 73 patients in the low LDH group (pre-treatment LDH Conclusion: LDH is of certain significance to the efficacy of first-line chemotherapy of small cell lung cancer. Higher LDH is a biomarker of poor clinical prognosis. The decrease of LDH after 2 cycles of first-line treatment may suggest longer PFS and OS for patients with SCLC. Patients with high pretreatment-LDH choosing EP treatment may have a longer PFS.

Plant mitochondrial fatty acid synthesis (mtFAS) appears to be important in photorespiration based on the reverse genetics research from Arabidopsis (Arabidopsis thaliana) in recent years, but its roles in plant development have not been completely explored. Here, we identified a tomato (Solanum lycopersicum) mutant, fern-like, which displays pleiotropic phenotypes including dwarfism, yellowing, curly leaves, and increased axillary buds. Positional cloning and genetic and heterozygous complementation tests revealed that the underlying gene FERN encodes a 3-hydroxyl-ACP dehydratase enzyme involved in mtFAS. FERN was causally involved in tomato morphogenesis by affecting photorespiration, energy supply, and the homeostasis of reactive oxygen species. Based on lipidome data, FERN and the mtFAS pathway may modulate tomato development by influencing mitochondrial membrane lipid composition and other lipid metabolic pathways. These findings provide important insights into the roles and importance of mtFAS in tomato development.

The development of facial recognition technology has become an increasingly powerful tool in wild animal individual recognition. In this paper, we develop an automatic detection and recognition method with the combinations of body features of big cats based on the deep convolutional neural network (CNN). We collected dataset including 12 244 images from 47 individual Amur tigers (Panthera tigris altaica) at the Siberian Tiger Park by mobile phones and digital camera and 1940 images and videos of 12 individual wild Amur leopard (Panthera pardus orientalis) by infrared cameras. First, the single shot multibox detector algorithm is used to perform the automatic detection process of feature regions in each image. For the different feature regions of the image, like face stripe or spots, CNNs and multi-layer perceptron models were applied to automatically identify tiger and leopard individuals, independently. Our results show that the identification accuracy of Amur tiger can reach up to 93.27% for face front, 93.33% for right body stripe, and 93.46% for left body stripe. Furthermore, the combination of right face, left body stripe, and right body stripe achieves the highest accuracy rate, up to 95.55%. Consequently, the combination of different body parts can improve the individual identification accuracy. However, it is not the higher the number of body parts, the higher the accuracy rate. The combination model with 3 body parts has the highest accuracy. The identification accuracy of Amur leopard can reach up to 86.90% for face front, 89.13% for left body spots, and 88.33% for right body spots. The accuracy of different body parts combination is lower than the independent part. For wild Amur leopard, the combination of face with body spot part is not helpful for the improvement of identification accuracy. The most effective identification part is still the independent left or right body spot part. It can be applied in long-term monitoring of big cats, including big data analysis for animal behavior, and be helpful for the individual identification of other wildlife species.

Plant height is an important target trait for crop genetic improvement. Our previous work has identified a salt-tolerant C2H2 zinc finger, SlZF3, and its overexpression lines also showed a semi-dwarf phenotype, but the molecular mechanism remains to be elucidated. Here, we characterized the dwarf phenotype in detail. The dwarfism is caused by a decrease in stem internode cell elongation and deficiency of bioactive gibberellic acids (GAs), and can be rescued by exogenous GA3 treatment. Gene expression assays detected reduced expression of genes in the GA biosynthesis pathway of the overexpression lines, including SlGA20ox4. Several protein–DNA interaction methods confirmed that SlZF3 can directly bind to the SlGA20ox4 promoter and inhibit its expression, and the interaction can also occur for SlKS and SlKO. Overexpression of SlGA20ox4 in the SlZF3-overexpressing line can recover the dwarf phenotype. Therefore, SlZF3 regulates plant height by directly repressing genes in the tomato GA biosynthesis pathway.

Domestication and improvement are important processes that generate the variation in genome and phonotypes underlying crop improvement. Unfortunately, during selection for certain attributes, other valuable traits may be inadvertently discarded. One example is the decline in fruit soluble solids content (SSC) during tomato breeding. Several genetic loci for SSC have been identified, but few reports on the underlying mechanisms are available. In this study we performed a genome-wide association study (GWAS) for SSC of the red-ripe fruits in a population consisting of 481 tomato accessions with large natural variations and found a new quantitative trait locus, STP1, encoding a sugar transporter protein. The causal variation of STP1, a 21-bp InDel located in the promoter region 1124 bp upstream of the start codon, alters its expression. STP1Insertion accessions with an 21-bp insertion have higher SSC than STP1Deletion accessions with the 21-bp deletion. Knockout of STP1 in TS-23 with high SSC using CRISPR/Cas9 greatly decreased SSC in fruits. In vivo and in vitro assays demonstrated that ZAT10-LIKE, a zinc finger protein transcription factor (ZFP TF), can specifically bind to the promoter of STP1Insertion to enhance STP1 expression, but not to the promoter of STP1Deletion, leading to lower fruit SSC in modern tomatoes. Diversity analysis revealed that STP1 was selected during tomato improvement. Taking these results together, we identified a naturally occurring causal variation underlying SSC in tomato, and a new role for ZFP TFs in regulating sugar transporters. The findings enrich our understanding of tomato evolution and domestication, and provide a genetic basis for genome design for improving fruit taste.

The causal gene, CaHY5 of a chemical induced green-hypocotyl mutant was identified by molecular mapping. CaHY5 regulates anthocyanin accumulation by directly binding to the promoter of genes in anthocyanin pathway. Morphological markers at seedling stage are useful indicators for F

The mechanisms underlying leafy heads in vegetables are poorly understood. Here, we cloned a quantitative trait locus (QTL) controlling leafy heads in lettuce (Lactuca sativa). The QTL encodes a transcription factor, SAWTOOTH 1 (LsSAW1), which has a BEL1-like homeodomain and is a homolog of Arabidopsis thaliana. A 1-bp deletion in Lssaw1 contributes to the development of leafy heads. Laser-capture microdissection and RNA-sequencing showed that LsSAW1 regulates leaf dorsiventrality and loss-of-function of Lssaw1 downregulates the expression of many adaxial genes but upregulates abaxial genes. LsSAW1 binds to the promoter region of the adaxial gene ASYMMETRIC LEAVES 1 (LsAS1) to upregulate its expression. Overexpression of LsAS1 compromised the effects of Lssaw1 on heading. LsSAW1 also binds to the promoter region of the abaxial gene YABBY 1 (LsYAB1), but downregulates its expression. Overexpression of LsYAB1 led to bending leaves in LsSAW1 genotypes. LsSAW1 directly interacts with KNOTTED 1 (LsKN1), which is necessary for leafy heads in lettuce. RNA-seq data showed that LsSAW1 and LsKN1 exert antagonistic effects on the expression of thousands of genes. LsSAW1 compromises the ability of LsKN1 to repress LsAS1. Our results suggest that downregulation or loss-of-function of adaxial genes and upregulation of abaxial genes allow for the development of leafy heads.

The hydraulic behaviour of the fractures in a fractured carbonate reservoir is a function of fracture intensity, aperture, intrinsic permeability, length, height and orientation, all of which influence the scale of connectivity and ultimately storage, productivity and reserves. If a geologically realistic fracture model is not appropriately incorporated into upscaled fracture properties for a dynamic simulation, it may still be possible to match a short production history, but calculations of field-wide fracture pore volumes and forecasts of future reservoir development may be poor and uncertain. To accurately represent the fractures, discrete fracture network (DFN) models were built and used to constrain fracture geometries and their hydraulic properties for use in forecasting, field development options and uncertainty characterization. The workflow illustrated in this paper shows how a DFN may be validated and calibrated through the simulation of transient bottom hole pressures from individual drill stem tests and pressure interference data, followed by upscaling to a full-field dynamic simulation model. This DFN-to-simulation workflow, applicable to most conventional fractured reservoirs, successfully matched reservoir pressure history for the field as a whole and for individual wells without having to locally modify any of the upscaled fracture properties around the wells. Sensitivity analysis identified key fracture drivers having the greatest impact upon the history match, and these were combined to produce history matched Low and High Case models. Production forecasts for the Low, Base and High Cases were used to predict reserves, manage risk and optimize the field development plan. Supplementary material: Supplementary figures are available at https://doi.org/10.6084/m9.figshare.c.5001203 Thematic collection: This article is part of the The Geology of Fractured Reservoirs collection available at: https://www.lyellcollection.org/cc/the-geology-of-fractured-reservoirs

The automatic individual identification of Amur tigers (Panthera tigris altaica) is important for population monitoring and making effective conservation strategies. Most existing research primarily relies on manual identification, which does not scale well to large datasets. In this paper, the deep convolution neural networks algorithm is constructed to implement the automatic individual identification for large numbers of Amur tiger images. The experimental data were obtained from 40 Amur tigers in Tieling Guaipo Tiger Park, China. The number of images collected from each tiger was approximately 200, and a total of 8277 images were obtained. The experiments were carried out on both the left and right side of body. Our results suggested that the recognition accuracy rate of left and right sides are 90.48% and 93.5%, respectively. The accuracy of our network has achieved the similar level compared to other state of the art networks like LeNet, ResNet34, and ZF_Net. The running time is much shorter than that of other networks. Consequently, this study can provide a new approach on automatic individual identification technology in the case of the Amur tiger.

Introduction The peritoneum is the most common metastatic site of gastric cancer and is associated with a dismal prognosis. However, there is no reliable biomarker for predicting peritoneal metastasis (PM). Materials and Methods Whole-exome sequencing (WES) was performed on formalin-fixed, paraffin-embedded (FFPE) samples from 63 patients with stage I-III gastric cancer and circulating tumor DNA (ctDNA) samples from 10 patients with stage IV gastric cancer. Differentially expressed genes (DEGs) were identified between the PM and non-PM groups and analyzed by multiple bioinformatics analyses. Univariate and multivariate Cox regression analyses were used to identify the risk factors for PM and a risk score model was developed. Results The number of mutant genes and the tumor mutation burden (TMB) in the PM group were higher than those in the non-PM group (p < 0.05). There was a significant positive correlation between the number of mutant genes and the TMB (R2 = 0.9997). The risk of PM was significantly higher in the high TMB group than in the low TMB group (p = 0.045). Forty-nine DEGs were identified as associated with PM in gastric cancer. CDC27 mutations were associated with a higher risk for PM and poor survival. The CDC27 mutations were located in the Apc3 region, the TPR region, and the phosphorylation region, and new mutation sites were not included in the TCGA database. Multivariable Cox regression analysis demonstrated that pathological T stage, poor tumor differentiation, Borrmann type, and CDC27 mutations were independent predictive factors of PM. A risk score model was constructed that demonstrated good performance. Conclusion Through WES, we identified 49 DEGs relevant to PM in gastric cancer. CDC27 mutations were independently associated with PM by statistical and bioinformatics analyses. A risk score model was built and was demonstrated to effectively discriminate gastric cancer patients with and without PM.

So far, there has been no safe and convenient method to weigh the large fierce animals, like Amur tigers. To address this problem, we built models to predict the body weight of Amur tigers based on the fact that body weight is proportional to body measurements or age. Using the method of body measurements, we extracted the body measurements from four different kinds of the lateral body image of tigers, i.e., total lateral image, central lateral image, ellipse fitting image and rectangle fitting image, and then we respectively used artificial neural network (ANN) and power regression model to analyze the predictive relationships between body weight and body measurements. Our results demonstrated that, among all ANN models, the model built with rectangle fitting image had the smallest mean square error. Comparatively, we screened power regression models which had the smallest Akakai information criteria (AIC). In addition, using the method of age, we fitted nonlinear regression models for the relationship between body weight and age and found that, for male tigers, logistic model had the smallest AIC. For female tigers, Gompertz model had the smallest AIC. Consequently, this study could be applied to estimate body weight of captive, or even wild, Amur tigers safely and conveniently, helping to monitor individual health and growth of the Amur tiger populations. This article is protected by copyright. All rights reserved.

We previously showed that the Arf1-mediated lipolysis pathway sustains stem cells and cancer stem cells (CSCs); its ablation resulted in necrosis of stem cells and CSCs, which further triggers a systemic antitumor immune response. Here we show that knocking down Arf1 in intestinal stem cells (ISCs) causes metabolic stress, which promotes the expression and translocation of ISC-produced damage-associated molecular patterns (DAMPs; Pretaporter [Prtp] and calreticulin [Calr]). DAMPs regulate macroglobulin complement-related (Mcr) expression and secretion. The secreted Mcr influences the expression and localization of enterocyte (EC)-produced Draper (Drpr) and LRP1 receptors (pattern recognition receptors [PRRs]) to activate autophagy in ECs for ATP production. The secreted ATP possibly feeds back to kill ISCs by activating inflammasome-like pyroptosis. We identify an evolutionarily conserved pathway that sustains stem cells and CSCs, and its ablation results in an immunogenic cascade that promotes death of stem cells and CSCs as well as antitumor immunity.

Roses are among the most economically important ornamental plants worldwide. But prickles on the stem and leaves cause difficulties for cultivation or inconveniences during harvest and transportation, thus are an undesirable horticultural character. However, little is known about the molecular mechanisms of prickle development. In this study, we sought to develop Rosa multiflora (in the family Rosaceae) as a model plant to study prickle formation. The morphology, structure, and ontogeny of prickles were characterized, and transcriptome analysis of prickly and prickleless R. multiflora genotypes was performed. Morphological observation and microscopic analyses revealed that prickles of R. multiflora were non-glandular prickles (NGPs) and their maturation went through five developmental stages, which was accompanied by the accumulation of secondary metabolites such as lignin and anthocyanins. Comparative transcriptome analysis identified key pathways and hub genes potentially involved in prickle formation. Interestingly, among the differentially expressed genes (DEGs), several notable development and secondary metabolism-related transcription factors (TFs) including NAC, TCP, MYB, homeobox, and WRKY were up-regulated in prickly internodes. KEGG enrichment analysis indicated that DEGs were enriched in the pathways related to biosynthesis of secondary metabolites, flavonoids, and phenylpropanoids in the prickly R. multiflora. Our study provides novel insights into the molecular network underlying the regulation of prickle morphogenesis in R. multiflora, and the identified candidates might be applied to the genetic improvement of roses.

e14556 Background: TIS is an anti-programmed cell death protein-1 antibody engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis. Primary results from this single-arm, multicenter, open-label, Phase 2 study evaluating TIS in pts with MSI-H/dMMR solid tumors, showed a clinically meaningful improvement in the objective response rate (ORR) for this patient population. Here we report results from the updated analysis (NCT03736889). Methods: Eligible adult pts with previously treated, locally advanced, unresectable/metastatic histologically confirmed MSI-H/dMMR solid tumors with ≥ 1 measurable lesion (RECIST v1.1) and an Eastern Cooperative Oncology Group performance status of ≤ 1 were enrolled. Pts received TIS 200 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or withdrawal. The efficacy analysis set were all pts who received any dose of TIS with measurable disease per independent review committee (IRC) at baseline. The primary endpoint was IRC-assessed ORR (RECIST v1.1). Secondary endpoints included duration of response (DoR), time to response (TTR), disease control rate (DCR), progression-free survival (PFS) (all IRC-assessed [RECIST v1.1]), overall survival (OS), and safety. Programmed death ligand 1 (PD-L1) immunohistochemistry assay (Ventana SP263) was applied retrospectively. Results: Between Sep 2018–Jul 2021, 80 pts were enrolled (median age 53 years; range 19–81 years) and 75 were included in the efficacy analysis set. In this updated efficacy analysis set, at a median follow-up of 15.2 months, ORRIRC was 46.7% (n = 35; 95% CI 35.1, 58.6) in all tumor types (1-sided p < 0.0001), including 5 complete responses (CR) and 30 partial responses (PR). ORRIRC was 39.1% (n = 18; 95% CI 25.1, 54.6) in colorectal cancer (CRC) pts (N = 46), 55.6% (n = 5; 95% CI 21.2, 86.3) in G/GEJC pts (N = 9), and 60.0% (n = 12; 95% CI 36.1, 80.9) in other pts (N = 20). Of the pts who responded (n = 35), one patient had disease progression. Median DoR was not reached, median TTRIRC was 11.9 weeks (range 8.4–98.9) and DCR was 72.0% (95% CI 60.4, 81.8). Median PFSIRC was not reached (95% CI 7.5, not estimable [NE]). Median OS (safety analysis set) was not reached (95% CI 28.7, NE). No clear association was observed between PD-L1 expression and clinical efficacy. Treatment-emergent adverse events (TEAEs) ≥ Grade 3 occurred in 48.8% (n = 39) of pts. The most common ≥ Grade 3 TEAE was anemia, 10.0% (n = 8). Immune-mediated TEAEs ≥ Grade 3 were 8.8% (n = 7). Conclusions: With a longer follow up time, TIS demonstrated clinically meaningful improvement in ORR in pts with MSI-H or dMMR solid tumors. TIS was generally well tolerated, with no new safety signals. These data support TIS as a new treatment option for this patient population. Clinical trial information: NCT03736889.

A total of 43 phyla (395 genera) of bacteria and 11 phyla (309 genera) of fungi were identified from normal sapwood (SW), wetwood (WW) and their transition zone wood (TW) in living poplar trees, with bacteria showing significantly higher diversity than fungi. Highly variable community diversities and compositions were found for bacteria but not for fungi among WW, TW and SW. Overall, 22 phyla (95 genera) bacteria and three phyla (11 genera) fungi were significantly different in relative abundance between WW and SW. Nine wood chemical properties were significantly correlated with the relative abundance of top 15 bacterial and fungal genera in all samples. Wetwood represents an abnormal condition of heartwood in living poplar trees. The cause of wetwood formation is still poorly understood, but it is generally considered to involve microbial activities. To facilitate a better understanding of wetwood formation, we sequenced the 16S rRNA and ITS (Internal Transcribed Spacer) genes of distinct regions (16S V4, ITS1) to precisely identify the microbial communities in normal sapwood (SW), wetwood (WW) and their transition zone wood (TW). Nine chemical properties of the wood samples were further determined to elucidate the correlations between the microbial communities and wood characteristics. The total sequences of 16S V4 and ITS1 from WW, TW and SW were assigned to 43 bacterial phyla (395 genera) and 11 fungal phyla (309 genera), indicating a significantly higher diversity of bacteria than fungi. Among SW, TW and WW, significant variations in community diversity and composition were found for bacteria but not for fungi. WW had the highest bacterial and lowest fungal diversities, while SW exhibited the highest fungal diversity. TW generally exhibited intermediate levels between WW and SW. Between WW and SW, 22 bacterial phyla (95 genera) were significantly different in relative abundance. Nine wood chemical properties were significantly correlated with the relative abundance of top 15 bacterial and fungal genera in all wood samples.

Mitochondria are crucial for the production of primary and secondary metabolites, which largely determine the quality of fruit. However, a method for isolating high-quality mitochondria is currently not available in citrus fruit, preventing high-throughput characterization of mitochondrial functions. Here, based on differential and discontinuous Percoll density gradient centrifugation, we devised a universal protocol for isolating mitochondria from the pulp of four major citrus species, including satsuma mandarin, ponkan mandarin, sweet orange, and pummelo. Western blot analysis and microscopy confirmed the high purity and intactness of the isolated mitochondria. By using this protocol coupled with a label-free proteomic approach, a total of 3353 nonredundant proteins were identified. Comparison of the four mitochondrial proteomes revealed that the proteins commonly detected in all proteomes participate in several typical metabolic pathways (such as tricarboxylic acid cycle, pyruvate metabolism, and oxidative phosphorylation) and pathways closely related to fruit quality (such as γ-aminobutyric acid (GABA) shunt, ascorbate metabolism, and biosynthesis of secondary metabolites). In addition, differentially abundant proteins (DAPs) between different types of species were also identified; these were found to be mainly involved in fatty acid and amino acid metabolism and were further confirmed to be localized to the mitochondria by subcellular localization analysis. In summary, the proposed protocol for the isolation of highly pure mitochondria from different citrus fruits may be used to obtain high-coverage mitochondrial proteomes, which can help to establish the association between mitochondrial metabolism and fruit storability or quality characteristics of different species and lay the foundation for discovering novel functions of mitochondria in plants.

Purpose: Patients with alveolar soft part sarcoma (ASPS) are rare and have few treatment options. We assessed the activity of geptanolimab (GB226), a fully humanized programmed cell death protein 1 antibody, for patients with unresectable, recurrent, or metastatic ASPS. Patients and Methods: We conducted this multicenter, single-arm, phase II study (Gxplore-005, NCT03623581) in patients aged 18–75 years who had unresectable, recurrent, or metastatic ASPS at 11 sites in China. Patients received intravenous geptanolimab (3 mg/kg) every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by independent review committee (IRC) per RECIST 1.1 in the full analysis set population. Results: Between September 6, 2018 and March 6, 2019, we enrolled and treated 37 patients with 23 (62.2%) having received prior systemic treatment. Fourteen [37.8%; 95% confidence interval (CI), 22.5–55.2] of 37 patients had an objective response assessed by IRC with a 6-month duration of response rate of 91.7%. Median progression-free survival was 6.9 months (95% CI, 5.0–not reached) and disease control was achieved in 32 (86.5%; 95% CI, 71.2–95.5) patients. Three of 37 patients reported grade 3 treatment-related adverse events (TRAEs), including anemia, hypophysitis, and proteinuria [one each (2.7%)]. No grade 4 TRAEs were observed. Two (5.4%) patients discontinued treatment due to TRAEs (one with hypophysitis and one with Mobitz type I atrioventricular block). The baseline percentage of CD4+ T cells was adversely associated with patient response (P = 0.031). Conclusions: Geptanolimab has clinically meaningful activity and a manageable safety profile in unresectable, recurrent, or metastatic ASPS.

Background: Human epidermal growth factor receptor 2 (ERBB2, HER-2) exon 20 insertion (ERBB2ex20ins) remains a refractory oncogenic driver in lung cancer. So far there is limited data showing the co-occurring mutation background of ERBB2ex20ins in Chinese lung cancer and its relationship with response to afatinib.Patients and Methods: A total of 112 Chinese patients with ERBB2ex20ins identified by next-generation sequencing from 17 hospitals were enrolled. The clinical outcomes of 18 patients receiving afatinib treatment were collected.Results: Among the 112 patients, insertion-site subtypes comprised of A775ins (71%; 79/112), G776indel (17%; 19/112), and P780ins (12%; 14/112). There were 66.1% (74/112) of patients carrying TP53 co-mutation and FOXA1 was the most prevalent co-amplified gene (5.5%, 3/55). The co-occurring genomic feature was similar among three insertional-site subtypes and had an overall strong concordance with the western population from the MSKCC cohort (R2 = 0.74, P < 0.01). For the prognosis, patients with co-occurring mutation in cell-cycle pathway especially TP53 showed shorter OS than patients without [median OS: 14.5 m (95% CI:12.7–16.3 m) vs. 30.3 m (95% CI: not reached), p = 0.04], while the OS was comparable among three subtypes. For the response to afatinib, ERBB2ex20ins as a subclonal variant was an independent factor relating to shorter PFS [median PFS: 1.2 m (95% CI: 0.8–1.6 m) vs. 4.3 m (95% CI: 3.3–5.3 m), p < 0.05].Conclusion: Our data revealed co-occurring TP53 represent an unfavorable prognosis of patients with ERBB2ex20ins, emphasizing the more valuable role of the co-mutation patterns than insertion-site subtypes in predicting prognosis of this group of patients. Moreover, the clonality status of ERBB2ex20ins was identified as a potential indicator for response to afatinib.