Multiomics in the central Arctic Ocean for benchmarking biodiversity change.

Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth.

Genomic landscape of treatment refractory metastatic colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis. MATERIAL AND METHODS: Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed. RESULTS: A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% (n = 72) of the patients. A total of 31.3% (n = 25) of the patients received therapy either as targetable therapy outside an available trial (n = 2), FDA approved therapy (n = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% (n = 21). CONCLUSION: Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy.

Percutaneous coronary intervention in patients hospitalized for non-ST-elevation myocardial infarction and the risk of postdischarge ischemic stroke at 6-month, 1-year, and 3-year follow-ups.

Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation myocardial infarction (NSTEMI) to reduce adverse cardiovascular events. However, the short- and long-term effects of PCI on the risk of postdischarge ischemic stroke (IS) in patients hospitalized for NSTEMI remain unclear. This study investigated the association of PCI on the risk of postdischarge IS in patients hospitalized for NSTEMI at different period follow-ups. A population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. Propensity score matching (PSM) was used to select 6079 pairs of the patients with NSTEMI treated invasively by PCI (received PCI during hospitalization) and initial conservative strategy (did not receive PCI during hospitalization) with similar baseline characteristics for evaluation. After adjustment for patients' clinical variables and the duration of dual antiplatelet therapy, PCI was associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups [adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.26-0.67, p < 0.001; aHR = 0.61, 95% CI 0.43-0.86, p = 0.004; and aHR = 0.69, 95% CI 0.54-0.89, p = 0.005respectively]. In the patients who had a CHA2DS2-VASc score of ≥2, PCI was also associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups (aHR = 0.54, 95% CI 0.36-0.83, p = 0.005; aHR = 0.72, 95% CI 0.52-1.00, p = 0.048; and aHR =0.73, 95% CI 0.58-0.91, p = 0.005, respectively). These findings suggested that PCI might reduce the risk of postdischarge IS in patients hospitalized for NSTEMI.

Comparative effect of antipsychotics on risk of self-harm among patients with schizophrenia.

OBJECTIVE: To investigate the association of different antipsychotic treatments with hospitalization due to self-harm among patients with schizophrenia. METHOD: This retrospective cohort study was based on Taiwan's universal health insurance database. Patients aged 15-45 years with a newly diagnosed schizophrenic disorder in 2001-2012 were included. The study outcome was the first hospitalization due to self-harm or undetermined injury after the diagnosis of schizophrenic disorders. The exposure status of antipsychotics was modeled as a time-dependent variable. The analyses were stratified by antipsychotic dosage based on defined daily dose (DDD). RESULTS: Among 70 380 patients with a follow-up of 500 355 person-years, 2272 self-harm hospitalization episodes were identified. Compared with none or former use, current use of several second-generation antipsychotics with a dose of one DDD or above, including amisulpride, aripiprazole, clozapine, risperidone, and sulpiride, was associated with decreased risk of self-harm hospitalization, with clozapine showing the strongest effect (adjusted rate ratio = 0.26, 95% confidence interval 0.15-0.47). CONCLUSION: The protective effect on self-harm may vary across different antipsychotics. Further studies are needed to replicate the findings.

Risk profiles of personality traits for suicidality among mood disorder patients and community controls.

OBJECTIVE: To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls. METHOD: We recruited 365 bipolar, 296 major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self-reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups. RESULTS: All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients. CONCLUSION: Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high-risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.

The Effects of Antidepressants and Quetiapine on Heart Rate Variability.

Introduction: The autonomic effects of antidepressants and quetiapine on heart rate variability (HRV) are inconsistent based on past studies. The aim of this study was to explore their influence on the HRV of psychiatric patients without psychotic symptoms. Methods: A total of 94 patients with depression, anxiety, or somatic symptoms, were recruited into this study. Based on their medication, 4 groups were identified: the no antidepressant group (n=19), the SSRI group (using sertraline or escitalopram, n=53), the other antidepressants group (using venlafaxine or mirtazapine, n=9), and the augmentation group (AG, using an antidepressant+quetiapine, n=13). The HRV of the 4 groups were compared. The correlations between HRV and the medication(s) used were clarified. Results: Among the 4 groups, the AG had the lowest HRV with its total power (TP), very low frequency power (VLF) and low frequency power (LF) of HRV being significantly different from those of the other groups. Age and using quetiapine were found to be negatively correlated with TP, VLF and LF. With this study group, the autonomic effects of antidepressants were found not to be significant. Discussion: Among psychiatric patients without psychotic symptoms, quetiapine causes an overt decrease in HRV.

Circulating immune-related proteins associated with immune checkpoint inhibitor efficacy in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Most patients with pancreatic ductal adenocarcinoma (PDAC) do not benefit from immune checkpoint inhibitor treatment. However, the phase II study CheckPAC (NCT02866383) showed a clinical benefit (CB) rate of 37% and a response rate of 14% in patients with metastatic PDAC receiving stereotactic radiation therapy and nivolumab with or without ipilimumab. Translational studies were initiated to characterize the patients who would benefit from this treatment. Here, we evaluated the association between treatment outcome and 92 circulating immuno-oncology-related proteins in patients from the CheckPAC trial. MATERIALS AND METHODS: The study included 78 patients with chemoresistant metastatic PDAC treated with nivolumab ± ipilimumab combined with radiotherapy. Proteins were measured in serum samples collected at baseline and on treatment with the use of the Olink Target 96 Immuno-Oncology panel. A cohort of 234 patients with metastatic PDAC treated with first-line chemotherapy were also included. RESULTS: High levels of Fas ligand (FASLG) and galectin 1 (Gal-1) and low levels of C-C motif chemokine 4 were associated with CB. High FASLG and Gal-1 were associated with longer progression-free survival in univariable analysis. In the multivariable Cox regression analysis, the association was significant for Gal-1 (P < 0.001) but not significant for FASLG (P = 0.06). A focused unsupervised hierarchal clustering analysis, including T-cell activation and immune checkpoint-related proteins, identified clusters of patients with higher CB rate and higher tumor expression of leukocyte or T-cell markers (CD3, CD45, granzyme B). Thirty-six proteins increased significantly during immunotherapy. Several proteins (including FASLG, checkpoint proteins, and immune activation markers) increased independently of response during immunotherapy but did not increase in the cohort of patients treated with chemotherapy. CONCLUSIONS: Circulating levels of immune-related proteins like FASLG and Gal-1 might be used to predict the efficacy of checkpoint inhibitors in patients with metastatic PDAC.

Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PICOG) that maximized discrimination of the predictive model. Patients with higher PICOG have higher predicted relapse risk. The PICOG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PICOG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PICOG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PICOG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PICOG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.

Extracorporeal membrane oxygenation as treatment for acute respiratory failure and subsequent pneumothorax caused by Pneumocystis jirovecii pneumonia in a kidney transplant recipient.

Acute respiratory failure (ARF) accompanied by pneumothorax caused by Pneumocystis jirovecii pneumonia (PJP) is often fatal. We present our experience using extracorporeal membrane oxygenation as treatment for ARF and subsequent pneumothorax caused by PJP in a kidney transplant recipient.

Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia.

Expression of Hoxa7 and Hoxa9 is activated by proviral integration in BXH2 murine myeloid leukaemias. This result, combined with the mapping of the HOXA locus to human chromosome 7p15, suggested that one of the HOXA genes might be involved in the t(7;11)(p15;p15) translocation found in some human myeloid leukaemia patients. Here we show that in three patients with t(7;11), the chromosome rearrangement creates a genomic fusion between the HOXA9 gene and the nucleoporin gene NUP98 on chromosome 11p15. The translocation produces an invariant chimaeric NUP98/HOXA9 transcript containing the amino terminal half of NUP98 fused in frame to HOXA9. These studies identify HOXA9 as an important human myeloid leukaemia gene and suggest an important role for nucleoporins in human myeloid leukaemia given that a second nucleoporin, NUP214, has also been implicated in human myeloid leukaemia.

Postoperative and long-term survival in relation to life-expectancy after pancreatic surgery in elderly patients (cohort study).

BACKGROUND: An evaluation of the outcome after pancreatic surgery with focus on post-operative and late survival in elderly patients was performed. METHODS: The study included 1.556 patients from a single HBP unit operated from 1. January 2010 to 31. December 2019. Patients were divided into two cohorts, < 75 years (n = 1.296) and ≥75 years (n = 260). Post-operative outcome was evaluated in all patients and late outcome in patients with adenocarcinoma in the pancreas (n = 765) and the duodenum (n = 117). The follow-up of patients with benign disease and adenocarcinoma was 57.95 (12.1-132.7) and 39.85 (12.0-131.7) months, respectively. RESULTS: Length of hospital-stay and surgical complications were not significantly different in the two cohorts, but in-hospital death was 1.1% (<75 years) and 3.5% (≥75 years) (p = 0.008). The median overall survival of adenocarcinoma was 29.7 (<75 years) and 24.3 months (≥75 years) (p = 0.3228) with a one, two, and five-years survival of 74.5%, 56.6% and 28.6% vs. 73.6%, 51.1%, and 25.5%. Median time to relapse (46.2% of patients <75 years and 40.5% of patients ≥75 years) was 9 (1 - 51) and 8 (1 - 78) months (p = 0.534), respectively. Adjuvant chemotherapy did not have impact on the survival of the old cohort. Patients who died during the observation period had lost 94% (<75 years) and 87% (≥75 years) of expected remnant life. Estimated years lost in the old cohort was 4.2 in males and 4.9 in females (p = 0.025). CONCLUSION: Elderly patients may undergo pancreatic surgery with a low mortality and for adenocarcinoma with an acceptable long-term survival.

Metagenome Sequencing to Explore Phylogenomics of Terrestrial Cyanobacteria.

Cyanobacteria are ubiquitous microorganisms with crucial ecosystem functions, yet most knowledge of their biology relates to aquatic taxa. We have constructed metagenomes for 50 taxonomically well-characterized terrestrial cyanobacterial cultures. These data will support phylogenomic studies of evolutionary relationships and gene content among these unique algae and their aquatic relatives.

Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus.

In B6AF1 mice, T lymphocytes that use the V beta 11-positive (and not V beta 6-positive or V beta 8-positive) segment in their receptor for antigen are greatly reduced in the thymus and peripheral lymphoid tissues, most likely as a result of clonal deletion. The relative number of V beta 11-positive cells in adult lymph nodes was ten times as high in B6AF1 mice thymectomized 1 to 4 days after birth as in normal mice. Moreover, for the first 10 days of life of B6AF1 mice, mature V beta 11-positive T cells were readily detected in the thymus and spleen. Thus neonatal thymectomy results in the maintenance of the receptor repertoire of early postnatal life, and this correlates with the subsequent development of organ-specific autoimmune diseases.

Thrombotic Ringed Polytetrafluoroethylene Graft With Infection After Living-Donor Liver Transplantation.

BACKGROUND: The safety of the living donor in living-donor liver transplantation (LDLT) is always the first priority, meanwhile, the graft-to-recipient weight ratio (GRWR) and the anatomy of the liver allograft must also not be compromised in order to warrant tranplatation success. When it comes to the allograft of the right lobe of the liver without the middle hepatic vein (R-M), the outflow and adequate drainage for the territory of middle hepatic vein (MHV) is one critical concern. Despite publications in some high-volume transplant centers on the positive results of using expanded polytetrafluoroethylene (ePTFE) grafts to substitute those of autologous veins, complications related to the ePTFE graft have not been well discussed. METHODS: From July 2012 to June 2016, 129 adult patients who underwent living donor liver transplantation in Taipei Veterans General Hospital were analyzed. There were 3 cases of adjacent organ erosion with gas bubbles in the lumen of an ePTFE graft, including gastrointestinal (GI) tract penetration in 2 out of the first 15 cases that used the venous graft of ringed expanded polytetrafluoroethylene (rPTFE). The patient survival rate during this period was compared and radiological findings of rPTFE function and clinical signs of erosion with infection were also examined to raise the concerns of safety as well as early detection of complications of rPTFE. RESULTS: The overall 1-year patient survival rate was 90%, of which the right lobe wih MHV (R+M) group was 93.5% and the R-M group was 91.9%. For the mean of GRWR, the R+M group was 1.05 ± 0.19 and R-M group was 1.19 ± 0.27, while those who needed reconstruction with vein grafts was 0.96 ± 0.11. Among the R-M group, 24 out of 88 cases (27.3%) needed reconstruction of MHV tributaries. Of the 24 cases, 15 cases were done with rPTFE and the 1-year patient survival rate of the rPTFE group was 73%, which is significantly worse (P = .008) than the non-rPTFE (89%) and non-reconstructed (97%) groups. The mean GRWR is significantly higher (P = .001) in the non-reconstructed group (1.19 ± 0.27) than in the rPTFE (0.99 ± 0.11) and non-rPTFE (0.94 ± 0.11) groups. The venous grafts patency rate between the different graft types is no different, and there is also significance in warm ischemic time (P = .009) between the non-reconstructed (49 ± 15), rPTFE (81 ± 51), and non-rPTFE (56 ± 18) groups in the mean minutes. CONCLUSION: In cases of fever of unknown cause in patients receiving LDLT with rPTFE graft, a regular computed tomography (CT) scan with contrast and gas bubbles within the graft lumen is the best way for early detection of graft related infection and suspicious GI tract penetration. To decrease the risks of tissue reaction induced by ePTFE graft in LDLT, omentum patches or other inert agents can be introduced as a buffer between the graft and adjacent organs, especially the GI tracts. However, research in material science shall be explored to solve the problem in the future.

A Novel Hybrid Viabahn-assisted Bypass Technique: Extra-arterial Flossing Wiring for Chronic Total Occlusion in Superficial Femoral Artery.

INTRODUCTION: A hybrid Viabahn-assisted bypass (VAB) technique is introduced for revascularizing chronic total occlusion (CTO) in superficial femoral artery (SFA) when bypass surgery is difficult or endovascular intervention fails. REPORT: This technique combines extra-arterial flossing wiring with antegrade-retrograde intervention via traditional open exposure of middle SFA and deploying a Viabahn from the proximal true lumen through the subintimal lumen and extra-arterial space, and back into distal true lumen to restore flow. It only needs a 3-5 cm incision to expose the mid-SFA without clamping or endarterectomy of the SFA. DISCUSSION: This hybrid procedure is an alternative technique to improve SFA revascularization in some difficult CTOs.

Microsatellite instability is not a defining genetic feature of acute myeloid leukemogenesis in adults: results of a retrospective study of 132 patients and review of the literature.

The frequency of acute leukemia in children with constitutional DNA repair defects implicates defective DNA repair in leukemogenesis. Whether sporadic cases of AML also arise from an inherited genetic predisposition remains to be determined. Prior studies have reported microsatellite instability (MSI) in AML, particularly secondary and relapsed AML. These studies included small numbers of cases in which key features such as cytogenetic abnormalities were not reported. To determine whether defective DNA mismatch repair, reflected by MSI, is a defining feature of adult myeloid leukemogenesis, we retrospectively studied 132 AML cases including 28 de novo, 62 secondary, 22 relapsed/refractory, 15 cases of paired diagnosis/relapse. 110 patients were elderly (55+ years). The cases included a range of cytogenetic abnormalities. MSI was assessed at three loci (BAT 25, BAT 26, BAT 40) in DNA isolated from sorted leukemic blasts and paired T cell controls. Fluoresceinated PCR products were analyzed using an automated capillary electrophoresis system. Of the 132 AML cases, no single case demonstrated MSI. Our studies indicate that MSI, and defective DNA mismatch repair, is not a defining feature of the majority of adult patients with AML. Furthermore, our data does not support the hypothesis that MSI could be acquired during the progression of AML from diagnosis to relapse, as a consequence of therapeutic exposure.

Multidrug resistance-1 (MDR1) expression and functional dye/drug efflux is highly correlated with the t(8;21) chromosomal translocation in pediatric acute myeloid leukemia.

Resistance to chemotherapy is a major problem in acute myeloid leukemia (AML). An important resistance mechanism in adult AML is active drug efflux mediated by the multidrug resistance protein-1 (MDR1). To determine if MDR1 is important in childhood AML, we examined MDR1 expression and functional dye/drug efflux in 20 pediatric/adolescent AML patients; results were correlated with cytogenetics and clinical outcome. Using flow cytometry, MDR1 protein expression on the leukemic blasts was measured with the antibody MRK16, while efflux was measured by extrusion of the fluorescent dye DiO(C2)3 in the presence/absence of cyclosporin A (CsA). Six of 20 cases expressed MDR1. While all six MDR1+ cases were efflux+, three of 14 MDR1- cases also demonstrated efflux. Both MDR1 and efflux were strongly correlated with the t(8;21). All six MDR1 +/efflux+ cases and 2/3 MDR1 -/efflux+ cases had a t(8;21), while no MDR1-/efflux- cases had a t(8;21) (P < 0.0005). This correlation between MDR1, efflux, and the t(8;21) in pediatric AML was not found in 11 adult t(8;21) cases similarly studied. Although the clinical relevance of MDR1 in pediatric AML awaits larger studies, our results suggest a biologic subset of pediatric AML patients may benefit from regimens which include MDR1-reversing agents or non-MDR1 substrates.

Lack of IRF-1 expression in acute promyelocytic leukemia and in a subset of acute myeloid leukemias with del(5)(q31).

One allele of interferon regulatory factor-1 (IRF-1), a transcriptional activator of genes critical for growth suppression, differentiation, and apoptosis, is usually deleted in acute myeloid leukemias (AML) and myelodysplasias (MDS) with deletion of chromosome 5q31. Accelerated exon skipping of IRF-1, resulting in transcripts lacking a translation initiation site, has been hypothesized as a means of functional inactivation of IRF-1 in AML/MDS. To test this hypothesis, we developed quantitative competitive RT-PCR assays to measure levels of full length and exon-skipped IRF-1 transcripts and measured IRF-1 proteins by Western blotting in a series of 45 samples of AML (13: -5/del5(q); 11: t(15;17); 7: t(8;21); and 7: inv(16)), normal blood and marrow, and myeloid cell lines. In contrast to AMLs with inv(16) or t(8;21), two AML samples with del(5q) had accelerated exon skipping and relatively low levels of full-length transcripts, while a third sample had very low transcript levels; IRF-1 proteins were not expressed and could not be induced by interferon gamma (IFNgamma). An additional six AML cases with -5/del(5q) had moderate exon-skipping and lacked constitutive IRF-1 proteins; however IRF-1 proteins were IFNgamma-inducible. Unexpectedly, all primary acute promyelocytic leukemia (APL) samples lacked IRF-1 protein and most exhibited accelerated exon skipping; furthermore, IRF-1 could not be induced by IFNgamma or all-trans retinoic acid (ATRA) which both induce IRF-1 in the NB4 APL cell line. Thus, accelerated exon skipping results in a loss of IRF-1 expression and function that cannot be overcome by exposure to inducing agents in a subset of AML patients with -5/del(5q) and in APL.

Patient and tumor characteristics of colon cancers with microsatellite instability: a population-based study.

Molecular screening for microsatellite instability (MSI) in colon cancers has been proposed to identify individuals with hereditary nonpolyposis colorectal cancer. To date, most reports of MSI in colorectal cancer have been based on studies of clinical case series or high-risk families. We examined the proportion of incident colon cancers in the general population that exhibit MSI by patient and tumor characteristics. We interviewed 201 colon cancer cases ascertained by the New Mexico Tumor Registry in the metropolitan Albuquerque area for demographic information, lifestyle factors, medical history, and family cancer history. Paired normal and tumor tissue specimens were obtained for each case. Three microsatellite markers were used; instability was defined as observed alteration at two or more loci. Overall, 37 of 201 (18%) colon cancers exhibited instability. MSI was more common among cases >70 years (26%) and most common among cases >80 years (38%). MSI was significantly associated with tumors in the proximal colon and with later stage and poor differentiation among cases >70 years. MSI was not associated with a history of polyps. Family history of colorectal cancer was associated with MSI only among cases <50 years. When all factors were analyzed jointly in a regression model, proximal subsite and poor differentiation remained significantly associated with MSI. One patient, whose tumor exhibited MSI, fulfilled the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer. Our study provides a population-based estimate of MSI in colon tumors and a representative estimate of the proportion of colorectal cancer patients in the general population who consent to be interviewed for family cancer history and to have biological samples analyzed.

bcl-2 gene rearrangement in salivary gland lymphoma.

There is a wide spectrum of lymphoid hyperplasias and neoplasias that may arise in salivary gland tissue. Some lesions arise in the extranodal mucosal-associated lymphoid tissue (MALT) located in the salivary gland; others arise within the lymph nodes embedded in the gland parenchyma. It is difficult to distinguish the site and cell of origin in many salivary gland lymphoid lesions, but recent advances in the identification of specific gene rearrangements in lymphomas corresponding to normal follicular center cells have provided a molecular marker for these tumors. The genes involved are the immunoglobulin heavy chain gene (located on chromosome 14) and the blc-2 gene (located on chromosome 18). This specific chromosomal translocation [t(14;18)] has been sought in extranodal lymphomas of skin, stomach, and intestine. To date, primary lymphomas in these sites have lacked the t(14;18) translocation. We investigated the t(14;18) using molecular techniques in a series of morphologically and immunophenotypically defined malignant non-Hodgkin's lymphomas presenting in the salivary gland. Of the seven cases we examined, three had molecular evidence of a t(14;18) translocation. All three lesions had a nodular growth pattern. The four cases lacking bcl-2 rearrangement had diffuse growth patterns. In addition, all four bcl-2 germline cases had morphologic or clinical findings consistent with a MALT origin. In contrast to the data published to date for primary lymphomas of the stomach, skin, and intestine, our findings indicate that salivary gland lymphomas frequently contain bcl-2 gene rearrangement. In addition, there appear to be differences in the clinical findings of bcl-2 rearranged and bcl-2 germline salivary gland lymphomas.