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Molecular targeted therapies are the standard of care for front‐line treatment of metastatic non‐small‐cell lung cancers (NSCLCs) harboring driver gene mutations. However, despite the initial dramatic responses, the emergence of acquired resistance is inevitable. Acquisition of secondary mutations in the target gene (on‐target resistance) is one of the major mechanisms of resistance. The mouse pro‐B cell line Ba/F3 is dependent on interleukin‐3 for survival and proliferation. Upon transduction of a driver gene, Ba/F3 cells become independent of interleukin‐3 but dependent on the transduced driver gene. Therefore, the Ba/F3 cell line has been a popular system to generate models with oncogene dependence and vulnerability to specific targeted therapies. These models have been used to estimate oncogenicity of driver mutations or efficacies of molecularly targeted drugs. In addition, Ba/F3 models, together with N‐ethyl‐N‐nitrosourea mutagenesis, have been used to derive acquired resistant cells to investigate on‐target resistance mechanisms. Here, we reviewed studies that used Ba/F3 models with EGFR mutations, ALK/ROS1/NTRK/RET fusions, MET exon 14 skipping mutations, or KRAS G12C mutations to investigate secondary/tertiary drug resistant mutations. We determined that 68% of resistance mutations reproducibly detected in clinical cases were also found in Ba/F3 models. In addition, sensitivity data generated with Ba/F3 models correlated well with clinical responses to each drug. Ba/F3 models are useful to comprehensively identify potential mutations that induce resistance to molecularly targeted drugs and to explore drugs to overcome the resistance. [ABSTRACT FROM AUTHOR]

Background: Approximately 10% of non‐small cell lung cancers (NSCLCs) that harbor epidermal growth factor receptor (EGFR) gene mutations have in‐frame insertions in exon 20 of the EGFR gene. These tumors do not usually respond to currently available EGFR‐tyrosine kinase inhibitors (TKIs). Tarloxotinib is a novel hypoxia‐activated prodrug that releases a potent, irreversible pan‐ERBB TKI (tarloxotinib‐E) under solid tumor hypoxia. Methods: We examined the efficacy of tarloxotinib‐E against several types of Ba/F3 cells with introduced EGFR exon 20 mutations (EGFR A763insFQEA, V769insASV, D770insSVD, H773insH and H773insNPH mutations). We assayed growth inhibition for tarloxotinib (prodrug), tarloxotinib‐E (active form), poziotinib, afatinib, and osimertinib in Ba/F3 cells with each EGFR exon 20 mutation. We also explored acquired resistance mechanisms to tarloxotinib‐E by establishing cells with resistance to tarloxotinib‐E via chronic drug exposure after N‐ethyl‐N‐nitrosourea mutagenesis treatment. Results: Among all tested Ba/F3 cell lines, IC50 was ≥72.1 times higher for tarloxotinib than for tarloxotinib‐E, which implies a wide therapeutic window with this prodrug strategy. Tarloxotinib‐E was efficacious against all tested Ba/F3 cells except for H773insH, which was less sensitive to all tested EGFR‐TKIs. As acquired resistance mechanisms to tarloxotinib‐E, we identified either T790M or C797S secondary mutations, depending on the original EGFR exon 20 mutation. Conclusions: These findings indicate that tarloxotinib‐E could be effective for NSCLC with EGFR exon 20 mutations. Our results also show that T790M or C797S mutations can confer acquired resistance to tarloxotinib‐E; and suggest that resistance mechanisms are influenced by the baseline EGFR exon 20 mutations. [ABSTRACT FROM AUTHOR]

Highlights • The treatment strategy for NSCLC with HER2 exon 20 insertion remains unclear. • Poziotinib showed potent activity against HER2 exon 20 insertions in vitro model. • C805S was identified as a mechanism underlying acquired resistance to poziotinib. • HSP90 inhibitors were able to overcome this resistant clone. Abstract Objectives Oncogenic HER2 mutations are present in 2–4% of lung adenocarcinomas, but the relevant clinical trials are unsatisfactory. The novel HER2 inhibitor poziotinib was recently developed and clinical trials are ongoing. We compared poziotinib with nine tyrosine kinase inhibitors (TKIs), and derived poziotinib-resistant clones to investigate the resistant mechanism. Materials and methods We introduced three common HER2 mutations A775_G776insYVMA (YVMA), G776delinsVC (VC) and P780_Y781insGSP (GSP), which account for 94% of HER2 exon 20 insertions in the literature, into Ba/F3 cells. We then compared the activity of poziotinib with that of nine TKIs (erlotinib, afatinib, dacomitinib, neratinib, osimertinib, AZ5104, pyrotinib, lapatinib, and irbinitinib), determined the 90% inhibitory concentration (IC 90) through a growth inhibition assay, and defined a sensitivity index (SI) as IC 90 divided by the trough concentration at the recommended dose as a surrogate for drug activity in humans. We also generated resistant clones by exposure to poziotinib in the presence of N-ethyl -N- nitrosourea, and HER2 secondary mutations that might serve as a resistance mechanism were searched. Results YVMA showed resistance to all tested drugs except neratinib, poziotinib and pyrotinib. Poziotinib was the only drug with an SI less than 10 for YVMA, the most common HER2 exon 20 insertion. We established 62 poziotinib-resistant clones, and among these, only C805S of HER2, which is homologous to C797S of the EGFR, was identified as a secondary mutation in 19 clones. We also revealed that heat shock protein (HSP) 90 inhibitors show potent anti-growth activity to the C805S secondary mutant clone. Conclusions Poziotinib showed the most potent activity against HER2 exon 20 mutations. We identified the secondary C805S at the covalent binding site of HER2 to poziotinib as a potential mechanism of acquired resistance. HSP90 inhibitors might be a therapeutic strategy for the C805S secondary mutation. [ABSTRACT FROM AUTHOR]

Endobronchial ultrasound (EBUS) is commonly used to guide transbronchial needle biopsies for the staging of lymph nodes in non-small cell lung cancer patients. Although contrast-enhanced ultrasound (CEUS) and microbubbles (MBs) can improve the diagnostic accuracy in tumors, the ability of contrast-enhanced EBUS (CE-EBUS) to image MBs has not yet been comprehensively evaluated. In this study, we assessed the ability of a CE-EBUS system (Olympus EU-ME2 PREMIER and BF-UC180F bronchoscope) to detect laboratory-synthesized MBs in comparison to clinical (Toshiba Aplio SSA-790A) and pre-clinical (VisualSonics Vevo 2100) CEUS systems in vitro and in vivo , respectively. Agar flow phantoms and reference tissue were used to assess CE-EBUS MB imaging in vitro, and A549 tumor-bearing athymic nude and AE17-OVA tumor-bearing C57BL/6 mice were used to assess MB detectability and perfusion in vivo , respectively. Results revealed that despite the lower sensitivity of CE-EBUS to MB concentration in comparison to clinical CEUS, CE-EBUS yielded a similar contrast-to-tissue ratio (CTR) in vitro of 28.9 ± 4.5 dB for CE-EBUS, compared with 29.7 ± 2.6 dB for clinical CEUS (p < 0.05). In vivo , CE-EBUS generated a perfusion curve highly correlated with that obtained with the pre-clinical CEUS system (Pearson correlation coefficient = 0.927, p < 0.05). Moreover, CE-EBUS yielded a CTR 2.7 times higher than that obtained with the pre-clinical ultrasound system. These findings together suggest that CE-EBUS can perform contrast imaging comparable to that produced by commercial pre-clinical and clinical ultrasound systems, with potential for clinical characterization of mediastinal lymph nodes in lung cancer patients. [ABSTRACT FROM AUTHOR]

• The inducibility of drug tolerant cells depended on the type of cell line. • Acquisition of DTC phenotype was a cellular response to high dose of EGFR-TKI. • High expression of RYK was a molecular mechanism of the drug-tolerant state. Emergence of acquired resistance is almost inevitable during EGFR-tyrosine kinase inhibitor therapy for non-small-cell lung cancer (NSCLC) harboring EGFR mutations. Drug tolerance, a reversible state of drug insensitivity in the early phases of tyrosine kinase inhibitor therapy, is considered to serve as the basis of recurrent disease. Therefore, it is important to elucidate the molecular mechanisms of drug tolerance. Five EGFR -mutated NSCLC cell lines were used in this study. We established drug-tolerant cells (DTCs) via 72 h treatment with osimertinib (600 nM) or afatinib (60 nM). Acquisition of drug tolerance was evaluated by growth inhibitory assay, and the molecular mechanisms of drug tolerance were analyzed by phospho-RTK array. DTCs were successfully induced in PC9, HCC4006, and H1975 cells against osimertinib and in PC9 cells against afatinib. We observed that a high drug concentration was required to induce DTCs, and HCC4006 cells become tolerant when a higher dose of afatinib (>180 nM) was used. In the analysis of HCC4006 DTCs against osimertinib, we observed increased receptor-like tyrosine kinase (RYK) expression, and siRNA-mediated RYK knockdown inhibited the proliferation of DTCs. These results suggest that induction of DTCs is dose-dependent, and increased RYK expression was the mechanism of drug tolerance in HCC4006 cells against osimertinib. [ABSTRACT FROM AUTHOR]

• Heterogeneity of EGFR-TKI resistance mechanisms will affect treatment strategy. • We found ten of 24 autopsied NSCLC patients developed heterogeneous resistance. • Patients with heterogeneous resistance mechanisms had shorter TTF (p = 0.0004). • T790M was frequently detected in locoregional lesions than distant metastases. • Three lost chance to use osimertinib; T790M (-) at biopsy but T790M (+) at autopsy. Overcoming acquired resistance against targeted therapies to improve outcomes of lung cancer patients harboring driver mutations is a critical issue. While drug therapy oriented to a resistance mechanism appears attractive, spatial heterogeneity of resistance mechanisms in each patient will diminish treatment efficacy. However, the frequency, clinical backgrounds, clinical implications, and patterns of spatial heterogeneity in resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) are largely unknown. This study included 128 specimens from 24 autopsied patients with lung adenocarcinoma harboring EGFR mutation. Acquired resistance mechanisms reported as relatively frequent in lung cancer, e.g. , T790 M and other secondary EGFR mutations, MET and ERBB2 gene amplification, and histological transformation, were retrospectively examined. All patients had received 1st/2nd generation EGFR-TKI and showed acquired resistance to the drug before death. No patient received osimertinib. No resistance mechanism was identified in two patients. T790M mutation was detected in 20 patients (83 %); however, nine of these patients also had lesions without T790M mutation. Among 22 patients whose resistance mechanisms were identified, ten had spatial heterogeneity of resistance mechanisms (45 %), and these patients had significantly shorter time-to-treatment failure compared with those without heterogeneity (median 4.7 months vs. 14.7 months, p = 0.0004). We observed significant spatial heterogeneity of acquired resistance mechanisms to EGFR-TKIs in lung adenocarcinoma. Our results also indicate that the incidence of resistance mechanisms may vary based on the biopsied tumor locations. [ABSTRACT FROM AUTHOR]

Highlights • Possible secondary resistant mutations against front-line osimertinib were examined. • Together with Del 19, only C797S conferred significant resistance to osimertinib. • Together with L858R, C797 and L718 mutations conferred resistance to osimertinib. • TKI sensitivities depended on combinations of secondary and activating mutations. Abstract Objectives Non-small cell lung cancers (NSCLCs) that harbor activating mutations for epidermal growth factor receptor (EGFR) show remarkable initial response to EGFR-tyrosine kinase inhibitors (TKIs), but inevitably acquire resistance, half of which are due to a T790 M secondary mutation when first-generation (1 G) or 2 G EGFR-TKIs are used. Osimertinib, a 3 G EGFR-TKI, is a standard of care in this situation, but eventually also evokes resistance, reportedly due to some tertiary EGFR mutations. However, the FLAURA trial showed the superiority of osimertinib over 1 G EGFR-TKIs in treatment-naïve patients, thus providing an option of first-line osimertinib treatment. Resistance in this setting is also inevitable, but its mechanism is unclear. We investigated whether resistance mutations that emerged with T790 M were responsible for the osimertinib resistance in the first-line setting; i.e. without T790 M, and if so, what treatment option was available. Materials and Methods We used literature search to identify EGFR mutations at codons L718, G724, L792, G796, and C797 as mechanisms of osimertinib resistance in the presence of T790 M. These mutations were introduced into Ba/F3 cells in cis with activating EGFR mutations but not with T790 M; inhibitory effects of five EGFR-TKIs were evaluated. Results Only C797S conferred significant resistance against osimertinib when exon 19 deletion was the activating mutation. However, co-existence of L858R with C797S, C797 G, L718Q, or L718 V mutations all conferred resistance to osimertinib. Erlotinib showed the greatest activity for C797S-mediated resistance. However, 2 G EGFR-TKIs (afatinib or dacomitinib) were effective for other resistance mutations. Conclusion After first-line osimertinib failure, 1 G or 2 G EGFR-TKIs are effective, depending on combinations of secondary and activating mutations. [ABSTRACT FROM AUTHOR]

Angioleiomyoma is a benign, pericytic (perivascular) neoplasm that primarily occurs in the subcutis or dermis of the extremities. The lesion typically presents as a small, firm, slow-growing, painful nodule. Magnetic resonance imaging reveals the lesion to be a well-defined, round to oval mass with signal intensity similar to or slightly hyperintense to that of skeletal muscle on T1-weightwed sequences. A dark reticular sign on T2-weighted sequences appears to be a characteristic feature of angioleiomyoma. Prominent enhancement is usually seen after intravenous contrast. Histologically, the lesion consists of well-differentiated smooth muscle cells with many vascular channels. Based on vascular morphologies, angioleiomyoma is classified into three subtypes: solid, venous, and cavernous. By immunohistochemistry, angioleiomyoma is diffusely positive for smooth muscle actin and calponin and variably for h-caldesmon and desmin. Conventional cytogenetic studies have demonstrated relatively simple karyotypes characterized by one or few structural rearrangements or numerical aberrations. In addition, metaphase comparative genomic hybridization analyses have revealed recurrent loss of 22q and gain of Xq. Angioleiomyoma can be successfully treated with simple excision, with a very low recurrence rate. Knowledge of this peculiar neoplasm is important because it can mimic a variety of benign and malignant soft-tissue tumors. This review provides an updated overview of the clinical, radiological, histopathological, cytogenetic, and molecular genetic features of angioleiomyoma., Competing Interests: The Authors declare no conflicts of interest associated with this article., (Copyright 2023, International Institute of Anticancer Research.)

Introduction: Recent studies have suggested that including presence or absence of ground-glass opacity (GGO) may improve the tumor descriptor (T descriptor) classification in clinical stage I NSCLC. In this study, we analyzed prognostic implications of presence or absence of GGO, size of the solid component, and predominant histology to identify the true prognostic determinant for early-stage NSCLC., Methods: We retrospectively examined 384 patients with clinical stage I NSCLC (solid: 242, part solid: 142) who underwent complete resection between 2009 and 2013., Results: Survival curves of the whole cohort revealed good separation using the current TNM classification. Nevertheless, the part-solid group had a favorable prognosis irrespective of solid component size. Conversely, patients in the solid tumor group with tumors between 3 and 4 cm had a worse prognosis than patients whose tumors were less than or equal to 3 cm. Thus, we propose the following novel T descriptor classification: IA, part-solid tumors; IB, solid tumors less than or equal to 3 cm; and IC, solid tumors between 3 and 4 cm. This novel classification system stratified patient prognosis better than the current classification. On pathologic evaluation, the part-solid group always had better prognoses than the solid group in each subgroup divided by pathologic grade., Conclusions: These results suggest that presence of GGO is the true prognostic determinant of stage I NSCLC, irrespective of the size of the solid component. Our novel T descriptor classification system could more accurately predict prognoses of clinical stage I NSCLC cases., (© 2022 The Authors.)

Background: HER2 ( ERBB2 ) activating mutations are present in 2-3% of lung adenocarcinomas; however, no targeted therapy is approved for HER2 -altered lung cancers. A novel pan-HER inhibitor, tarloxotinib, is designed to release the active form (tarloxotinib-E) under hypoxic conditions in tumor tissues after being administered as a prodrug. Following the evaluation of the in vitro activity of tarloxotinib-E in HER2 -mutant cells, we explored the mechanisms of resistance to tarloxotinib-E in these cells., Methods: Growth inhibitory assays were performed with tarloxotinib-E and its prodrug using Ba/F3 cells expressing one of six HER2 mutations or wild-type (WT) HER2 , in addition to H1781 cells with HER2 exon 20 insertions. Resistant clones were established from N-ethyl-N-nitrosourea (ENU)-treated HER2 -mutant Ba/F3 cells and H1781 cells by chronic exposure to tarloxotinib-E., Results: Tarloxotinib-E showed potent activity against HER2 -mutant Ba/F3 cells and H1781 cells. Furthermore, the half maximal inhibitory concentration (IC 50 ) of tarloxotinib (inactive form) for WT HER2 was 180 times higher than that of tarloxotinib-E, indicating a wide therapeutic window of tarloxotinib. We established 30 resistant clones with secondary mutations of HER2 by ENU mutagenesis, all of which harbored C805S in exon 20. In the analysis of H1781 cells that acquired resistance to tarloxotinib-E, we found that increased HER3 expression was the molecular mechanism of tarloxotinib-E resistance., Conclusions: Tarloxotinib-E exhibited potent activity against cell line models with HER2 mutations. We identified a secondary C805S HER2 mutation and HER3 overexpression as the mechanisms of acquired resistance to tarloxotinib-E., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-216). Dr. TM serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. Dr. TK has received research funding from Boehringer Ingelheim outside the submitted work. Dr. KS has received research funding from Rain Therapeutics and Boehringer Ingelheim, an honorarium from Boehringer Ingelheim, AstraZeneca, and Chugai outside the submitted work, and has been on the advisory board of AstraZeneca. Dr. TF has received research funding from Apollomics and an honorarium form Novartis outside the submitted work. Dr. AH has received lecture fees from AstraZeneca and Chugai outside the submitted work. Dr. VT and Mr. AV are currently employees of rain therapeutics and own stock in rain therapeutics. Dr. RCD is currently an employee of Rain Therapeutics and owns stock in Rain Therapeutics and has received personal fees from Genentech/Roche, Ignyta, Blueprint Medicines, Green Peptide, AstraZeneca, Anchiano, Takeda/Millenium, and Bayer outside the submitted work; in addition, Dr. RCD has a patent for U.S. Provisional Patent Application No. 62/712,531 pending and licensed to Rain Therapeutics. The University of Colorado has received licensing fees from Foundation Medicine, Ignyta, Scorpion Therapeutics, Voronoi, Pearl River, Black Diamond Therapeutics, and Genentech for biologic materials derived in Dr. RCD’s laboratory. Dr. TM has received research funding from Astra Zeneca, Boehringer Ingelheim, Chugai, Taiho, Ono Pharmaceutical, Merck Sharp and Dohme, and Eli-Lilly; has been on the advisory board of Novartis, AstraZeneca, Amgen, Janssen pharma, Merck Sharp and Dohme and Puma Biotech; has received lecture fees from AstraZeneca, Boehringer Ingelheim, Novartis, Chugai, Pfizer, Bristol-Myers Squibb, Eli Lilly, Merck Sharp and Dohme, Ono Pharmaceutical, Merck Biopharma and Takeda, outside the submitted work. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Background: Recent studies of advanced lung cancer patients have shown that circulating tumor DNA (ctDNA) analysis is useful for molecular profiling, monitoring tumor burden, and predicting therapeutic efficacies and disease progression. However, the usefulness of ctDNA analysis in surgically resected lung cancers is unclear., Methods: This study included 20 lung cancer patients with clinical stage IIA-IIIA disease. Preoperative and postoperative (3-12 days) plasma samples were collected for ctDNA analysis. Cancer personalized profiling by deep sequencing, which can detect mutations in 197 cancer-related genes, was used for ctDNA detection. The cohort consisted of 18 men and 2 women with a median age of 69 (range, 37-88) years. Sixteen patients (80%) had a history of smoking. Histologically, there were four squamous cell carcinomas, 13 adenocarcinomas, two adenosquamous cell carcinomas, and one small cell carcinoma., Results: At the time of data analysis, the 20 patients had been monitored for a median follow-up of 12 months. Eight patients (40%) were positive for preoperative ctDNA, and this was significantly correlated with tumor size (≥5 vs . <5 cm, P=0.018). Four patients (20%) were positive for postoperative ctDNA, and this was significantly correlated with histological grade (3 vs . 1 or 2, P=0.032). Postoperative positivity for ctDNA also predicted shorter recurrence-free survival (RFS) (P=0.015), while pre- and post-operative carcinoembryonic antigen levels (P=0.150 and P=0.533, respectively) and preoperative positivity for ctDNA (P=0.132) were not correlated with RFS., Conclusions: Detecting ctDNA postoperatively was a poor prognostic factor in surgically resected lung cancer patients that may suggest there is minimal residual disease (MRD)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-505). TM serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. Dr. Suda reports personal fees from AstraZeneca, grants and personal fees from Boehrinnger-Ingelheim, grants from Rain Therapeutics, outside the submitted work. Dr. Sakai reports personal fees from Roche Diagnostics, Bio-Rad, SRL Diagnostics, AstraZeneca, and Chugai Pharmaceutical, outside the submitted work. TF reports personal fees from Novartis, grants from Apollomics.Inc., outside the submitted work. KN reports grants and personal fees from Otsuka Pharmaceutical, Life Technologies Japan, Boehringer Ingelheim, and Eli Lilly; personal fees from Chugai Pharmaceutical, Eisai, from Pfizer, Novartis, MSD, Ono Pharmaceutical, Bristol-Myers Squibb, SymBio Pharmaceuticals Limited, Solasia Pharma, Yakult Honsha, Roche Diagnostics, AstraZeneca, Sanofi, Guardant Health, Takeda, and Kobayashi Pharmaceutical, grants from Ignyta, and Astellas, outside the submitted work. TM reports grants and personal fees from AstraZeneca, Boehrinnger-Ingelheim, and Pfizer, personal fees from MSD, grants and personal fees from Chugai, grants and personal fees from Ono, personal fees from Eli-Lilly, grants and personal fees from Daiiichi-Sankyo, personal fees from ThermoFisher, personal fees from Guardant, grants and personal fees from Taiho, personal fees from Amgen, and Novartis, outside the submitted work. The other authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Purpose: Solid tumors show increased interstitial fluid pressure (IFP), which correlates to a number of pathophysiological features of tumors. There have been no reports on the usefulness of measuring IFP in lung cancer. The aim of this study was to examine the relationship between IFP and the clinicopathological characteristics of lung cancer., Methods: IFP was measured prospectively in 215 patients with 219 lesions showing solid or part-solid appearance. Four patients with double lung cancer were excluded from the analysis, resulting in 211 patients with lung cancer being analyzed for the correlation between IFP and computed tomography (CT) appearance, size, Tumor-node-metastasis (TNM) classification, maximal standardized uptake value (SUVmax), histological type, tumor grade, pleural and vessel invasion, Ki-67 index, and recurrence-free survival (RFS)., Results: The mean IFP was 8.5 mmHg; IFP was significantly correlated with the tumor size, SUVmax, TNM, vessel and pleural invasion, and Ki-67 index. Low IFP was associated with a better RFS compared to high IFP. Multivariate analysis did not select IFP as independent prognostic factor. In subgroup analysis of patients with adenocarcinoma, IFP was selected as independent one., Conclusions: IFP correlates clinicopathological factors of lung cancer. IFP might be used as a prognostic factor for lung cancer.

Elastofibroma is a rare, benign, slow-growing degenerative pseudotumor that typically occurs in the subscapular region and has been considered a peculiar fibroblastic proliferation with accumulation of abnormal elastic fibers. Very little is known about the cytogenetic and molecular genetic changes in elastofibroma. In the present study, we analyzed DNA copy number changes in 27 elastofibromas by comparative genomic hybridization. DNA was extracted from 22 archival paraffin-embedded tumor tissues and from 5 fresh frozen samples. Nine (33%) of the 27 cases exhibited DNA copy number changes involving one or two chromosomes, whereas the remaining 18 cases exhibited no DNA copy number changes. The majority of the changes were gains (8 cases), whereas 2 cases showed losses. The most common recurrent gains were at chromosomal locations Xq12-q22 (6 cases) and 19 (2 cases). High-level amplifications and recurrent losses were not observed. There was no correlation between DNA copy number changes and the pseudotumor size. The present study has identified a chromosomal region that may contain genes involved in the development of at least some elastofibromas.