Utility of synthetic MRI in predicting pathological complete response of various breast cancer subtypes prior to neoadjuvant chemotherapy.

AIM: To evaluate the usefulness of synthetic magnetic resonance imaging (MRI) performed before the initiation of neoadjuvant chemotherapy (NAC) in predicting whether breast cancers can achieve a pathological complete response (pCR) after the completion of NAC. MATERIALS AND METHODS: This retrospective study investigated 37 consecutive patients with 39 breast cancers (pCR: 14, and non-pCR: 25) who underwent dynamic contrast-enhanced (DCE)-MRI and synthetic MRI before the initiation of NAC. Using synthetic MRI images, quantitative values (T1 and T2 relaxation times, proton density [PD] and their standard deviations [SD]) were obtained in breast lesions, before (Pre-T1, Pre-T2, Pre-PD, SD of Pre-T1, SD of Pre-T2, SD of Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD, SD of Gd-T1, SD of Gd-T2, SD of Gd-PD) contrast agent injection. The aforementioned quantitative values and several morphological features that were identified on DCE-MRI were compared between pCR and non-pCR. RESULTS: Multivariate analyses revealed that the SD of Pre-T2 (p=0.038) was significant and was an independent predictor of pCR, with an area under the receiver operating characteristics curve of 0.829. The sensitivity, specificity, and accuracy of the SD of Pre-T2 with an optimal cut-off value of 11.5 were 71.4%, 80%, and 76.3%, respectively. CONCLUSIONS: The SD of Pre-T2 obtained from synthetic MRI was used successfully to predict those breast cancers that would achieve a pCR after the completion of NAC; however, these results are preliminary and need to be verified by further studies.

Utility of synthetic MRI in predicting the Ki-67 status of oestrogen receptor-positive breast cancer: a feasibility study.

AIM: To evaluate the utility of synthetic magnetic resonance imaging (MRI) of the breast in predicting the Ki-67 status in patients with oestrogen receptor (ER)-positive breast cancer. MATERIALS AND METHODS: Forty-nine patients with 50 histopathologically proven breast cancers who underwent additional synthetic MRI were enrolled in the present study. Using synthetic MRI images, T1 and T2 relaxation times and their standard deviations (SD) in the breast lesions before (T1-Pre, T2-Pre, PD-Pre, SD of T1-Pre, SD of T2-Pre, SD of PD-Pre) and after (T1-Gd, T2-Gd, PD-Gd, SD of T1-Gd, SD of T2-Gd, SD of PD-Gd) contrast agent injection were obtained. These quantitative values were compared between the low Ki-67 expression (<14%) lesions (low-proliferation group: n=23) and high Ki-67 expression (≥14%) lesions (high-proliferation group: n=27). RESULTS: The univariate analysis showed that the SD of T1-Gd (p<0.001) and T2-Gd (p=0.042) were significantly higher in the high-proliferation group than in the low-proliferation group. Multivariate analysis further showed that the SD of T1-Gd was a significant and independent predictor of Ki-67 expression, with an area under the receiver operating characteristic (AUROC) curve of 0.885. The sensitivity, specificity, and accuracy of the SD of T1-Gd with an optimal cut-off value of 98.5 were 77.8%, 87%, and 82%, respectively. CONCLUSION: The SD of T1-Gd obtained from synthetic MRI was useful to predict Ki-67 status.

Long-term results of concurrent chemoradiotherapy with daily-low-dose continuous infusion of 5-fluorouracil and cisplatin (LDFP) for Stage I-II esophageal carcinoma.

We investigated long-term treatment outcomes and the feasibility of chemoradiotherapy consisting of daily-low-dose 5-fluorouracil and cisplatin (LDFP) chemotherapy plus radiotherapy for Stage I-II squamous cell esophageal cancer. Treatment records from the 2000 through 2008 period were reviewed retrospectively. Fractionated radiotherapy was performed with a total dose of 60 Gy delivered in 2 Gy per fraction. LDFP chemotherapy, as continuous infusion of 200 mg/m2 5-fluorouracil combined with one hour infusion of 4 mg/m2 cisplatin, was administered on the same days as radiotherapy. Survival was calculated by the Kaplan-Meier method. Survival, responses, failure patterns, and toxicities were evaluated. Seventy-six (47 stage I and 29 stage II) patients were analyzed with a median follow-up of 93.6 months. The 8-year overall survival (OS), progression-free survival (PFS) and cause-specific survival (CSS) rates were 63.4%, 49.8%, and 76.7%, respectively. The 8-year OS, PFS, and CSS for stage I and stage II patients were 71.0%/56.1%/82.9% and 45.2%/40.2%/66.6%, respectively. Sixty-eight patients (89.5%) completed the treatment regimen. A complete response (CR) was achieved in 68 patients (89.5%). Twenty-five patients (36.8%) experienced recurrence after CR. The failure patterns were (overlap included): local failure (n = 12), nodal metastasis (n = 12), distant metastasis (n = 3), details unknown (n = 2). Salvage therapy was performed for local failure; endoscopic therapy (n = 7) or surgery (n = 2). Six patients remain alive without relapse after salvage endoscopic therapy. Major Grade 3 or higher acute adverse events were leukopenia (22%), anorexia (17%), and esophagitis (11%). Major late toxicities (Grade 3 or 4) involved pericardial effusion (12%), pleural effusion (4%), and esophageal stenosis (3%). Chemoradiotherapy with LDFP provided favorable long-term survival with acceptable toxicity for Stage I-II squamous cell esophageal cancer. The tumor response was excellent, but close endoscopic follow-up is essential for detecting and treating local recurrence.

Foetal development of the human gluteus maximus muscle with special reference to its fascial insertion.

The human gluteus maximus muscle (GMX) is characterised by its insertion to the iliotibial tract (a lateral thick fascia of the thigh beneath the fascia lata), which plays a critical role in lateral stabilisation of the hip joint during walking. In contrast, in non-human primates, the GMX and biceps femoris muscle provide a flexor complex. According to our observations of 15 human embryos and 11 foetuses at 7-10 weeks of gestation (21-55 mm), the GMX anlage was divided into 1) a superior part that developed earlier and 2) a small inferior part that developed later. The latter was adjacent to, or even continuous with, the biceps femoris. At 8 weeks, both parts inserted into the femur, possibly the future gluteal tuberosity. However, depending on traction by the developing inferior part as well as pressure from the developing major trochanter of the femur, most of the original femoral insertion of the GMX appeared to be detached from the femur. Therefore, at 9-10 weeks, the GMX had a digastric muscle-like appearance with an intermediate band connecting the major superior part to the small inferior mass. This band, most likely corresponding to the initial iliotibial tract, extended laterally and distally far from the muscle fibres. The fascia lata was still thin and the tensor fasciae latae seemed to develop much later. It seems likely that the evolutionary transition from quadripedality to bipedality and a permanently upright posture would require the development of a new GMX complex with the iliotibial tract that differs from that in non-human primates. (Folia Morphol 2018; 77, 1: 144-150).

Role of prostaglandin D2 and CRTH2 blockade in early- and late-phase nasal responses.

BACKGROUND: Prostaglandin D2 (PGD2 ) plays an important role in allergic inflammation. The PGD2 receptor, CRTH2, is expressed on basophils, eosinophils, and Th2 lymphocytes and mediates chemotactic activity. OBJECTIVE: To define the role of CRTH2 in allergen-induced nasal responses in a mouse model of allergic rhinitis (AR), a potent, selective CRTH2 receptor antagonist, ARRY-063 was administered in a model of allergic rhinitis in mice. METHODS: ARRY-063 was administered orally to ovalbumin (OVA) sensitized and challenged mice. To assess nasal obstruction, respiratory frequency (RF) was monitored by whole-body plethysmography immediately after the 4th challenge (early-phase response, EPR) and 24 h after the 6th challenge (late-phase response, LPR). Nasal resistance (RNA ) was also measured in the LPR. PGD2 was administered with or without OVA to determine the effect of PGD2 on nasal responsiveness. Cytokine levels and histopathological changes in nasal tissue were analysed. RESULTS: Instillation of PGD2 in the nose of sensitized mice together with a low concentration of OVA induced both an EPR and LPR. Treatment with the CRTH2 receptor antagonist prevented the decreases in RF seen immediately following the 4th challenge of sensitized mice (EPR). In the LPR, decreases in RF and increases in RNA were also prevented by antagonist treatment associated with reduced cytokine levels and inflammation in nasal tissues. CONCLUSIONS: These data identify PGD2 as a mediator of both the EPR and LPR in this model of AR and suggest that antagonism of CRTH2 prevents the development of both the EPR and LPR as well as nasal inflammation.

Tmem2 Deficiency Leads to Enamel Hypoplasia and Soft Enamel in Mouse.

Teeth consist of 3 mineralized tissues: enamel, dentin, and cementum. Tooth malformation, the most common craniofacial anomaly, arises from complex genetic and environmental factors affecting enamel structure, size, shape, and tooth eruption. Hyaluronic acid (HA), a primary extracellular matrix component, contributes to structural and physiological functions in periodontal tissue. Transmembrane protein 2 (TMEM2), a novel cell surface hyaluronidase, has been shown to play a critical role during embryogenesis. In this study, we demonstrate Tmem2 messenger RNA expression in inner enamel epithelium and presecretory, secretory, and mature ameloblasts. Tmem2 knock-in reporter mice reveal TMEM2 protein localization at the apical and basal ends of secretory ameloblasts. Micro-computed tomography analysis of epithelial-specific Tmem2 conditional knockout (Tmem2-CKO) mice shows a significant reduction in enamel layer thickness and severe enamel deficiency. Enamel matrix protein expression was remarkably downregulated in Tmem2-CKO mice. Scanning electron microscopy of enamel from Tmem2-CKO mice revealed an irregular enamel prism structure, while the microhardness and density of enamel were significantly reduced, indicating impaired ameloblast differentiation and enamel matrix mineralization. Histological evaluation indicated weak adhesion between cells and the basement membrane in Tmem2-CKO mice. The reduced and irregular expressions of vinculin and integrin ß1 suggest that Tmem2 deficiency attenuated focal adhesion formation. In addition, abnormal HA accumulation in the ameloblast layer and weak claudin 1 immunoreactivity in Tmem2-CKO mice indicate impaired tight junction gate function. Irregular actin filament assembly was also observed at the apical and basal ends of secretory ameloblasts. Last, we demonstrated that Tmem2-deficient mHAT9d mouse ameloblasts exhibit defective adhesion to HA-containing substrates in vitro. Collectively, our data highlight the importance of TMEM2 in adhesion to HA-rich extracellular matrix, cell-to-cell adhesion, ameloblast differentiation, and enamel matrix mineralization.

Prediction of nodal metastasis based on intraoral sonographic findings of the primary lesion in early-stage tongue cancer.

The aim of this study was to clarify the correlation between imaging findings obtained using intraoral ultrasonography (US) and pathological findings of tongue cancers, and to examine the predictive value of intraoral US findings with respect to occult nodal metastasis. This was a retrospective study based on the medical records of 123 patients with T1-2N0 tongue cancer. The depth of invasion (DOI) on intraoral US was positively correlated with the pathological invasion depth (PID) (ρ = 0.7080, P < 0.0001). Receiver operating characteristic analyses revealed an optimal DOI cut-off value of 4.1 mm and optimal PID cut-off value of 3.9 mm to detect nodal metastasis. Regarding the margin shape of the primary tumour on intraoral US, the incidence of nodal metastasis was significantly higher for the permeated type than for the pressure type (P < 0.001) and wedge-shaped type (P = 0.002). Furthermore, tumours with peritumoural vascularity assessed by power Doppler US had a significantly higher incidence of nodal metastasis than tumours without (P = 0.003). The sensitivity, specificity, and accuracy of the permeated type to predict nodal metastasis was 53.6%, 95.8%, and 86.2%, respectively. These results suggest that intraoral US findings closely reflect pathological findings and could be useful to predict occult nodal metastasis in patients with early-stage tongue cancer.

Pre-operative endovascular coil embolisation for chronic pulmonary aspergillosis.

OBJECTIVE: To retrospectively evaluate the clinical outcomes of pre-operative endovascular coil embolisation (ECE) for chronic pulmonary aspergillosis (CPA).METHODS: We evaluated surgical patients with CPA between November 2016 and April 2020. Pre-operative ECE for CPA with severe adhesions was selectively performed to reduce intra-operative blood loss. ECE procedures, operative procedures, intra-operative blood loss and complications were evaluated.RESULTS: Twenty-eight patients (21 males and 7 females; median age: 55 years) were included in the study. Of the 28 patients, 8 (28.6%) underwent pre-operative ECE. Technical success rate in pre-operative ECE was 100%. The median time required for ECE procedures was 123 min. The median number of vessels embolised per procedure was 2.5. The median period between embolisation and surgery was 5 days. Major complications were observed in three patients (10.7%). There were no significant differences between patients with and without pre-operative ECE in operative time (284 vs. 365 min, respectively, P = 0.7602) and intra-operative blood loss (294 vs. 228 mL, respectively, P = 0.8987).CONCLUSIONS: Pre-operative ECE for CPA appears to be feasible and safe; however, its role in reducing intra-operative blood loss needs further investigation.

A genetically defined signature of responsiveness to erlotinib in early-stage pancreatic cancer patients: Results from the CONKO-005 trial.

BACKGROUND: high recurrence rates of up to 75% within 2 years in pancreatic ductal adenocarcinoma (PDAC) patients resected for cure indicate a high medical need for clinical prediction tools and patient specific treatment approaches. Addition of the EGFR inhibitor erlotinib to adjuvant chemotherapy failed to improve outcome but its efficacy in some patients warrants predictors of responsiveness. PATIENTS AND METHODS: we analysed tumour samples from 293 R0-resected patients from the randomized, multicentre phase III CONKO-005 trial (gemcitabine ± erlotinib) with targeted sequencing, copy number, and RNA expression analyses. FINDINGS: a total of 1086 mutations and 4157 copy-number aberrations (CNAs) with a mean of 17.9 /tumour were identified. Main pathways affected by genetic aberrations were the MAPK-pathway (99%), cell cycle control (92%), TGFß signalling (77%), chromatin remodelling (71%), and the PI3K/AKT pathway (65%). Based on genetic signatures extracted with non-negative matrix factorization we could define five patient clusters, which differed in mutation patterns, gene expression profiles, and survival. In multivariable Cox regression analysis, SMAD4 aberrations were identified as a negative prognostic marker in the gemcitabine arm, an effect that was counteracted when treated with erlotinib (DFS: HR=1.59, p = 0.016, and OS: HR = 1.67, p = 0.014). Integration of differential gene expression analysis established SMAD4 alterations with low MAPK9 expression (n = 91) as a predictive biomarker for longer DFS (HR=0.49; test for interaction, p = 0.02) and OS (HR = 0.32; test for interaction, p = 0.001). INTERPRETATION: this study identified five biologically distinct patient clusters with different actionable lesions and unravelled a previously unappreciated association of SMAD4 alteration status with erlotinib effectiveness. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that SMAD4 status might guide addition of erlotinib treatment in early-stage PDAC patients.

[Thoracoplasty].

Thoracoplasty was at 1st invented for the treatment of pulmonary tuberculosis during the days when no effective chemotherapeutic drugs for tuberculosis were available. Removal of some portions of the ribs by thoracoplasty deforms the chest wall and compresses tuberculous cavities. Since the introduction of potent anti-tuberculous drugs, thoracoplasty for pulmonary tuberculosis has been obsolete. Currently, thoracoplasty is mainly applied to reduction of the volume of the pleural space in the treatment of post-resectional space problems and in the treatment of thoracic empyema. Well-planned and safe resections of the affected ribs hold the keys to successful thoracoplasty. The procedure is performed alone or with muscle flaps or with omental flap, depending on the extent of space and the presence of bronchopleural fistula. Thoracic surgeons should know the current application of thoracoplasty.

Normalization by cell fusion of sister chromatid exchange in Bloom syndrome lymphocytes.

Fusion of fresh lymphocytes from a Bloom syndrome (BS) patient with those of normal subjects or a BS heterozygote resulted in complete normalization of the frequency of sister chromatid exchanges in the chromosomes of BS cells. This normalization took place by the first mitosis in hybrid cells. In contrast, cultivation of BS lymphocytes with those of normal subjects or the BS heterozygote had no effect on sister chromatid exchanges. The cell fusion experiments suggest that the normalization on the sister chromatid exchanges. The cell fusion experiments suggest that the normalization of the sister chromatid exchange frequencies in BS cells can be achieved by factors conserved in the cells of various mammalian species. These findings are compatible with the concept that BS is a recessive genetic mutation at regulatory levels of the DNA repair function.

Clinical comparison of two different types of bifurcated graft for postoperative baPWV and ABI.

AIM: A newly-designed bifurcated graft with the distal end larger than the conventional type has been developed. The purpose of this study was to evaluate the early results of graft replacement using this new graft, and to compare whether the new graft is more advantageous than the conventional graft in terms of peripheral blood flow and arterial stiffness. METHODS: Records of 36 patients who underwent bifurcated graft replacement for infrarenal abdominal aortic aneurysm (AAA), from May 2003 to September 2006 were reviewed after excluding peripheral arterial disease (ABI > 0.9). Subjects were divided into two groups: group C (N.=20), with implantation of the conventional type and group N (N.=16), with implantation of the new type. We investigated changes in brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI), measurements being performed preoperatively and postoperatively. RESULTS: baPWV in the postoperative group as a whole was significantly higher than in the preoperative group (P<0.05), while ABI in the postoperative group was lower than in the preoperative group (P<0.05). In group C, baPWV increased (P<0.05) and ABI decreased (P<0.05) after bifurcated graft replacement, whereas in group N, there were no significant differences in changes of baPWV and ABI. CONCLUSIONS: This study shows that the new graft reduces the development of arterial stiffness postoperatively compared with the conventional type. These results may predict the new type graft decrease in the risk of morbidity and mortality caused by atherosclerotic disease.

[Locally advanced non-small cell lung cancer completely resected after induction therapy].

We analyzed 8 patients with unresectable locally advanced non-small cell lung cancer who responded to chemotherapy or chemoradiotherapy and underwent complete resection between June 2003 and June 2005. The patients were all male with a mean age of 61 years (range, 42 to 72 years). Histological subtypes included adenocarcinoma in 4 patients and squamous cell carcinoma in 4 patients. Clinical staging included T2N2M0 in 3 patients, T2N3M0 in 2 patients, and 1 patient each for T3N2M0, T4N2M0, and T4N3M0. Preoperative treatment included chemotherapy in 5 patients and chemoradiotherapy in 3 patients, all of whom had a partial response. Surgical procedures included lobectomy in 6 patients and pneumonectomy in 2 patients. In addition, all of the patients underwent mediastinal lymph node dissection (ND2a). Pathological effect included Ef. 0 in 1 patient, Ef. 1 in 2 patients, Ef. 2 in 2 patients, Ef. 3 in 3 patients. The median survival time from initial treatment (or surgery) was 16 (14) months in all cases, 22 (19) for ycN0, 12 (8) for ycN2, 31 (27) for Ef. 3, 13 (9) for Ef. 0-2, 27 (23) for pN0, 13 (9) for pN1-3, 31 (27) for chemoradiotherapy, 16 (13) for chemotherapy, 24 (21) for adenocarcinoma, and 15 (11) for squamous cell carcinoma. Multimodality treatment, including surgery, is beneficial for patients with unresectable locally advanced non-small cell lung cancer who respond to chemotherapy or chemoradiotherapy, especially those patients with ycN0 or pN0.

[21-year-old man with squamous cell carcinoma of the lung].

Lung cancer among people in their twenties is rare and accounts for only 0.1-0.4% of all cases. We describe a case of squamous cell carcinoma of the lung in a 21-year-old man. The otherwise healthy patient presented with a 1 month history of cough. Chest radiography showed a well-defined round mass 5 cm in size in the right lower lobe. Computed tomography also showed a 3 cm hilar lymph node. Bronchoscopy revealed a white polypoid mass obstructing the right basal bronchus. Transbronchial biopsy revealed poorly differentiated squamous cell carcinoma of the lung. Clinical diagnosis was T2N1M0, stage IIB lung cancer. Right lower lobectomy with mediastinal lymph node dissection was performed. Lymph node metastases were proven histologically in the pretracheal, subcarinal, hilar, and intrapulmonary regions. Pathological diagnosis was T2N2M0, stage IIIA lung cancer. Endobronchial and mediastinal lymph node metastases were found 2 months after surgery. He received 3 rounds of chemotherapy with cisplatin and docetaxel and irradiation to the right hilum and mediastinum at a total dose of 60 Gy in 30 fractions. He is alive 6 months after surgery.

[Endobronchial neurinoma treated with left lower lobectomy].

Benign endobronchial tumors are rare, and among these endobronchial neurinoma is extremely rare. We describe a case of endobronchial neurinoma successfully treated with left lower lobectomy. A 58-year-old man presented with an 8-month history of cough. During this period he was repeatedly treated with antibiotics for pneumonia of the left lower lobe. Chest X-ray showed atelectasis of the left lower lobe. Computed tomography (CT) of the chest showed a mass in the left main and lower lobe bronchi. Bronchoscopy revealed the mass almost completely obstructing the left main bronchus. Although transbronchial biopsy was inconclusive and yielded necrotic tissue with Aspergillus hyphae, lung cancer was highly suspected based on clinical and radiographic findings. He underwent left lower lobectomy and was discharged 14 days after surgery in good condition. Pathological diagnosis was an endobronchial neurinoma 4 cm in size arising from the left basal bronchus. On immunohistochemical staining, the tumor was positive for S-100 protein and negative for a-smooth muscle actin. He took itraconazole at a daily dose of 200 mg orally for 6 months. He remains well 52 months after surgery without any evidence of recurrence.

[Diffuse malignant pleural mesothelioma].

Malignant pleural mesothelioma is an uncommon neoplasm that caused 647 deaths in Japan in 2004. The incidence of the disease is increasing and is estimated to reach its peak in 2025. We reviewed the clinical features in 11 consecutive patients with pathologically confirmed diffuse malignant pleural mesothelioma in our institution from January 1997 to December 2002. Of the 11 patients, 9 were male and 2 were female with a mean age of 66 (range, 55 to 90) years. Symptoms included dyspnea in 4 patients, chest pain in 3, dyspnea plus chest pain in 2, and cough in 2. Median period between symptom onset and presentation was 1 (range, 0 to 6) month. A history of asbestos exposure was identified in 3 patients and suspected in 5. A definitive diagnosis was made by closed pleural biopsy in 8 patients, pleural fluid cytology in 2, and autopsy in 1. Histological subtypes included epithelioid in 6 patients, sarcomatoid in 2, biphasic in 1, and unknown in 2. International Mesothelioma Interest Group (IMIG) staging included stage II in 6 patients, stage III in 3, and stage IV in 2. Median period between presentation and diagnosis was 1 (range, 0 to 22) month. Treatment included intrapleural chemotherapy in 4 patients, extrapleural pneumonectomy in 3, pleural drainage in 2, and best supportive care in 2. During the follow-up period, 9 patients died and 2 survived. Median survival time after diagnosis was 3 (range, 0 to 51) months. Of the 11 patients, 7 (64%) died within 6 months after the first presentation, and only 1 (9%) lived longer than 2 years after diagnosis.

Identification of cell-type-specific mutations in nodal T-cell lymphomas.

Recent genetic analysis has identified frequent mutations in ten-eleven translocation 2 (TET2), DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 2 (IDH2) and ras homolog family member A (RHOA) in nodal T-cell lymphomas, including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified. We examined the distribution of mutations in these subtypes of mature T-/natural killer cell neoplasms to determine their clonal architecture. Targeted sequencing was performed for 71 genes in tumor-derived DNA of 87 cases. The mutations were then analyzed in a programmed death-1 (PD1)-positive population enriched with tumor cells and CD20-positive B cells purified by laser microdissection from 19 cases. TET2 and DNMT3A mutations were identified in both the PD1+ cells and the CD20+ cells in 15/16 and 4/7 cases, respectively. All the RHOA and IDH2 mutations were confined to the PD1+ cells, indicating that some, including RHOA and IDH2 mutations, being specific events in tumor cells. Notably, we found that all NOTCH1 mutations were detected only in the CD20+ cells. In conclusion, we identified both B- as well as T-cell-specific mutations, and mutations common to both T and B cells. These findings indicate the expansion of a clone after multistep and multilineal acquisition of gene mutations.

Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia.

Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17). Age, hemoglobin concentration and white blood cell counts were correlated with the number of mutations. Patients with mutations ⩾6 showed higher rate of achieving major molecular response than those<6 (P=0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were significantly enriched with cell signaling and cell division pathways. Furthermore, DNA copy number analysis showed that 2 of 24 patients had uniparental disomy of chromosome 1p or 3q, which disappeared major molecular response was achieved. These mutations may play significant roles in CML pathogenesis in addition to the strong driver mutation BCR-ABL1.