Variant allele frequencies do not correlate well with myeloblast counts in a clinically validated gene sequencing panel for routine acute myeloid leukemia workup.

Next generation sequencing (NGS) has introduced new types of data, such as variant allele frequencies (VAFs), into the workup of acute myeloid leukemias (AML). There is interest in using NGS to prognosticate disease behavior and monitor residual disease, but the attribution of sequencing data entirely to the leukemic clone may be confounded by VAF contribution from background non-leukemic populations and undetected copy number aberrations. Sixty-eight patients with AML were evaluated by a clinically validated gene sequencing panel at our institution from 2015 to 2018. No correlation was found with a direct comparison of blast counts and VAFs in both primary- and secondary-AML (R2 = 0.0584 and 0.0235, respectively). Only moderate correlations were attained when evaluating against mutant NPM1 allele fraction alone (R2 = 0.5303) or when variants with allelic frequencies >55% of the blast burden were excluded (R2 = 0.4608). VAFs from regular clinical-use gene sequencing panels show poor unrestricted correlation with leukemic blast proportions in AML.

Non-small cell lung cancers with isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations.

Isocitrate dehydrogenases 1 and 2 (IDH1/2) are important metabolic enzymes that convert isocitrate to α-ketoglutarate. IDH1/2 mutations are associated with the development of multiple malignancies. In this study, we examine the prevalence and features of non-small cell lung cancers (NSCLC) with IDH1/2 mutations. From May 2013 to March 2017, 800 lung cancer samples were successfully sequenced for somatic mutations on the Ion Torrent PGM with the 50-gene AmpliSeq Cancer Hotspot Panel v2 on the Ion Torrent PGM (318 chip). Variants were identified using the Ion Torrent Variant Caller Plugin and reference genome hg19. Golden Helix's SVS software was used for variant annotation and prediction of significance. Nine samples (1.1%) from 8 patients harbored an IDH1 (3 p.R132C and 2 p.R132L) or IDH2 mutation (p.R140W, p.R172S, and p.R172T). All patients' tumors had adenocarcinoma histology, and all patients had a smoking history. Eighty-eight percent of patients' tumors had a coexisting KRAS mutation and 6 of 8 were diagnosed at greater than 70 years of age. Five patients presented with stage IV disease and 3 with stage I. After comparison to a cohort of KRAS-mutated NSCLC with a history of smoking, IDH-mutated cases were significantly older but presented with similar rates of advanced-stage disease and sex distribution. Additional studies are needed to understand the role of IDH1/2 mutations in the development of NSCLC, but such patients who have poor prognostic indicators (KRAS mutation and advanced stage at presentation) may benefit from IDH1/2-directed therapies.

A rare cause of postoperative hypotension.

A 62-year-old woman presented with a 3-month history of abdominal distension and decreased exercise tolerance. A chest radiograph showed a probable left pleural effusion (Fig 1). A CT scan of the abdomen revealed a solid ovarian mass with omental caking and a large volume of ascites; there was also confirmation of a left pleural effusion. Three days before surgery a CT pulmonary angiogram (CTPA) showed no evidence of pulmonary thromboembolism (PTE). The patient had some improvement in her symptoms after paracentesis and thoracentesis with drainage of 2,000 mL and 250 mL of fluid, respectively. She underwent total abdominal hysterectomy, bilateral oophorectomy, and partial sigmoid resection with an estimated blood loss of 850 mL. During the operation, she received 5 L of crystalloid and required phenylephrine at 40 to 80 µg/min to maintain a mean arterial pressure > 65 mm Hg. She was extubated after surgery, but immediately after extubation, she became markedly hypotensive and hypoxemic with a BP of 50/20 mm Hg and an oxygen saturation of 70%. An ECG showed T-wave inversions from V1 to V5 and an S1Q3T3 pattern (Fig 2). A bedside echocardiogram showed an enlarged right ventricle (RV), septal dyskinesia, and obliteration of the left ventricle, all consistent with systolic and diastolic RV overload (Fig 3).