Endometriosis is a significant risk factor for clear cell and endometrioid ovarian cancers and is often found contiguous with these cancers. Using whole-genome shotgun sequencing of seven clear cell ovarian carcinomas (CCC) and targeted sequencing in synchronous endometriosis, we have investigated how this carcinoma may evolve from endometriosis. In every case we observed multiple tumour-associated somatic mutations in at least one concurrent endometriotic lesion. ARID1A and PIK3CA mutations appeared consistently in concurrent endometriosis when present in the primary CCC. In several cases, one or more endometriotic lesions carried the near-complete complement of somatic mutations present in the index CCC tumour. Ancestral mutations were detected in both tumour-adjacent and -distant endometriotic lesions, regardless of any cytological atypia. These findings provide objective evidence that multifocal benign endometriotic lesions are clonally related and that CCCs arising in these patients progress from endometriotic lesions that may already carry sufficient cancer-associated mutations to be considered neoplasms themselves, albeit with low malignant potential. We speculate that genomically distinct classes of endometriosis exist and that ovarian endometriosis with high mutational burden represents one class at high risk for malignant transformation.

Refrigerated dough is a flour‐based, unbaked product that is stored between 4 and 7C. The aim of this work was to study the rheological properties of refrigerated dough during storage and determine their correlations with dough proteins. Rheological properties were determined using texture analyzer and dynamic oscillatory rheometry during 34 days of storage. The protein analysis was performed by size‐exclusion high performance liquid chromatography. On day 34, Rmax was 93.8% higher than day 0. Both, the G′and G″moduli decreased during storage. Dough exhibited the major decreases on the moduli on day 3 and day 16. By comparing the viscoelastic properties of day 0 and day 16, a 50% decrease on the elastic modulus and a roughly 30% decrease in the loss modulus were observed. Changes in the protein fractions of dough samples were related to their rheological properties. The high and low molecular weight polymeric protein and gliadin were positively correlated to dough extensibility (r > 0.8343). PRACTICAL APPLICATIONS By definition, refrigerated dough is a flour‐based, unbaked product that is stored between 4 and 7C. Today's refrigerated dough industry traces its origin to a small bakery that started business in Louisville, KY in 1937. The first refrigerated dough product was a chemically leavened biscuit with a shelf life of about 3 weeks. Today, the refrigerated dough market encompasses a wide range of products available in the U.S.A. as well as the international market, including Western Europe and Canada. There are very limited peer review articles on the topic. This study investigated the stability of refrigerated dough during storage. The results obtained in the present work showed that protein composition of dough is altered during storage and these changes affect the rheological properties of dough samples. We believe that the refrigerated dough industry will find the presented research very useful in their applications.

A prospective study was conducted to identify biomarkers associated with resistance to panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). Patients with previously treated, codon 12/13 KRAS wt, mCRC were prospectively administered panitumumab 6 mg/kg IV q2weeks. Of 34 panitumumab-treated patients, 11 (32%) had progressive disease at 8 weeks and were classified as non-responders.A Nanostring nCounter-based assay identified a 5-gene expression signature (ERBB2, MLPH, IRX3, MYRF, and KLK6) associated with panitumumab resistance (P = 0.001). Immunohistochemistry and in situ hybridization determined that the HER2 (ERBB2) protein was overexpressed in 4/11 non-responding and 0/21 responding cases (P = 0.035). Two non-responding tumors had ERBB2 gene amplification only, and one demonstrated both ERBB2 amplification and mutation. A non-codon 12/13 KRAS mutation occurred in one panitumumab-resistant patient and was mutually exclusive with ERBB2/HER2 abnormalities.This study identifies a 5-gene signature associated with non-response to single agent panitumumab, including a subgroup of non-responders with evidence of aberrant ERBB2/HER2 signaling. KRAS wt tumors resistant to EGFRi may be identified by gene signature analysis, and the HER2 pathway plays an important role in resistance to therapy.

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T he mechanism for electrocardiographic (ECG) abnormalities in the setting of acute pancreatitis remains unknown. We present a case involving a patient diagnosed with acute pancreatitis who had ECG findings suggestive of inferior ST-segment elevation myocardial infarction (STEMI) with concordant inferior wall motion abnormalities on echocardiography and patent coronary arteries. CASE PRESENTATIoNA 78-year-old man presented to a peripheral hospital after experiencing 2 h of nonexertional epigastric pain with progressive radiation to his chest. This was associated with nausea and diaphoresis, but no dyspnea, palpitations or presyncope. Electrocardiography was performed and revealed ST-segment elevation in the inferior leads suggestive of myocardial infarction (MI) ( Figure 1A). The patient was transferred for cardiac catheterization. Physical examination of the patient revealed a diffusely distended abdomen with tympanic bowel sounds, but no signs of peritonitis. Although acute pancreatitis was suspected, the authors decided to proceed with coronary angiography to determine whether there was concomitant occlusion of a coronary artery. A minimal amount of contrast agent was used. Coronary angiography was only notable for calcified nonobstructive lesions in the left anterior descending artery (40% to 50%) and right coronary artery (20% to 30%) ( Figures 1B and 1C). The left circumflex artery was small in size, supplied a small territory and had only mild narrowing. Echocardiography revealed hypokinesis of the inferior wall with mild reduction in right ventricular function (Figure 2). Subsequent electrocardiography demonstrated resolution of the ST-segment elevation (Figure 3). Mild electrocardiographic abnormalities are often observed in the setting of acute pancreatitis. The authors report a case involving a patient diagnosed with acute pancreatitis who had electrocardiographic findings of ST-elevation myocardial infarction with concordant echocardiographic findings of wall motion abnormalities, but patent coronary arteries and no evidence of myocardial injury on pathology. key Words: Acute pancreatitis; ECG abnormalities; ST elevationThis open-access article is distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC) (http:// creativecommons.org/licenses/by-nc/4.0/), which permits reuse, distribution and reproduction of the article, provided that the original work is properly cited and the reuse is restricted to noncommercial purposes. For commercial reuse, contact support@pulsus.com