Phosphorus (P) is an essential macronutrient for algal communities, but in excess can exacerbate stream eutrophication. However, P loadings to streams vary temporally from continuous to episodic as a ...result of inputs from point and non-point sources, respectively. P loading pattern can thus alter the temporal availability of P and may influence effects of P enrichment on algal communities. We assessed how P loading pattern influences algal biomass and composition by conducting a 29-day P enrichment experiment in nine artificial streams exposed to either: (1) continuous P enrichment; (2) episodic P enrichment, or; (3) no P enrichment. P enrichment increased algal biomass accrual, but peak biomass did not differ between continuously and episodically enriched treatments. Maximum absolute growth rates were also comparable between P enriched treatments. However, episodic P additions sustained elevated rates of biomass accrual, whereas absolute growth rates in the continuously enriched communities declined towards the end of the experiment. P enrichment resulted in comparable increases in relative abundance of chlorophytes and decreased proportions of bacillariophytes and charophytes in algal communities for continuously and episodically enriched treatments. However, composition of bacillariophyte (diatom) assemblages differed significantly among all P enrichment treatments in accordance with species autecological attributes for P. Our results demonstrate that episodic and continuous P enrichment may augment algal biomass similarly. Yet, P loading pattern regulated the composition of algal communities. Thus, remedial management strategies for the control of nuisance algae production may require focus on the predominant source of P to streams. Finally, species specific responses of diatom assemblages to P enrichment and associated loading patterns suggests this taxonomic group may have potential as diagnostic indicators for identifying the presence of key nutrient sources associated with eutrophication of stream ecosystems.
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•Temporal patterns of phosphorus delivery may influence benthic algae communities.•Artificial streams simulated continuous and episodic phosphorus enrichment.•Phosphorus delivery pattern altered species composition but not biomass.•Short-duration phosphorus pulses can structure stream algal communities.•Stream management may benefit by addressing episodic phosphorus enrichment.
In this brief report, we provide an analysis of the influence of a novel CYP2C haplotype (CYP2C:TG) on proton pump inhibitor (PPI) pharmacokinetics (PK) in children. The CYP2C:TG haplotype has been ...proposed to be associated with increased CYP2C19 activity. We sought to determine if this CYP2C:TG haplotype resulted in similar alterations in metabolism for proton pump inhibitors, which are primarily metabolized by CYP2C19. In a cohort of 41 children aged 6–21 participating in a PPI pharmacokinetic study, effects of the CYP2C:TG allele were assessed by fitting two linear regression models for each of the six PK outcomes assessed, the second of which accounted for the presence of the CYP2C:TG allele. The difference in R2 values between the two models was computed to quantify the variability in the outcome that could be accounted for by the CYP2C:TG allele after adjustment for the CYP2C19 genotype. We found the CYP2C:TG haplotype to have no measurable additive impact on CYP2C19‐mediated metabolism of PPIs in vivo in older children and adolescents. The findings of this study do not support the clinical utility of routine testing for the CYP2C:TG haplotype to guide PPI dose adjustments in children.
Objectives: Prognostically relevant chromosomal abnormalities in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are routinely identified by fluorescence in situ hybridization ...(FISH) on peripheral blood or bone marrow specimens. We studied the prevalence of chromosomal abnormalities on extramedullary tissues involved by CLL/ SLL and evaluated their association with prominent proliferation centers (PPCs). Methods: FISH for recurrent abnormalities in CLL/SLL was performed on formalin- fixed, paraffin-embedded biopsy sections. PPCs were identified on H&E-stained sections. Available FISH results on peripheral blood or bone marrow specimens were also reviewed. Results: Recurrent FISH abnormalities were detected in 69% of 320 CLL/SLL biopsy specimens studied, including +12 (35%), 13q- (24%), 11q- (15%), 17p- (6%), 6q- (2%), and IGH/ BCL2 (0.9%). Forty-three patients had abnormal blood or bone marrow FISH analyses, of whom 7 (16%) had discordant +12 and/or 13q-, and 3 (7%) had discordant 17p- or 11q-. Morphology was positive (17%), negative (78%), or equivocal (6%) for PPCs on 247 evaluable biopsy specimens, a finding not significantly associated with FISH results (P = .7). Conclusions: Trisomy 12 is overrepresented in tumoral CLL/SLL involvement, compared with the known predominance of 13q- in blood. Discrepancies between leukemic and tissue FISH findings are occasionally encountered. FISH results do not correlate with the presence of PPCs. KEY WORDS Chronic lymphocytic leukemia; Small lymphocytic lymphoma; Fluorescence in situ hybridization
Abstract
Objectives
Prognostically relevant chromosomal abnormalities in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are routinely identified by fluorescence in situ ...hybridization (FISH) on peripheral blood or bone marrow specimens. We studied the prevalence of chromosomal abnormalities on extramedullary tissues involved by CLL/SLL and evaluated their association with prominent proliferation centers (PPCs).
Methods
FISH for recurrent abnormalities in CLL/SLL was performed on formalin-fixed, paraffin-embedded biopsy sections. PPCs were identified on H&E-stained sections. Available FISH results on peripheral blood or bone marrow specimens were also reviewed.
Results
Recurrent FISH abnormalities were detected in 69% of 320 CLL/SLL biopsy specimens studied, including +12 (35%), 13q– (24%), 11q– (15%), 17p– (6%), 6q– (2%), and IGH/BCL2 (0.9%). Forty-three patients had abnormal blood or bone marrow FISH analyses, of whom 7 (16%) had discordant +12 and/or 13q–, and 3 (7%) had discordant 17p– or 11q–. Morphology was positive (17%), negative (78%), or equivocal (6%) for PPCs on 247 evaluable biopsy specimens, a finding not significantly associated with FISH results (P = .7).
Conclusions
Trisomy 12 is overrepresented in tumoral CLL/SLL involvement, compared with the known predominance of 13q– in blood. Discrepancies between leukemic and tissue FISH findings are occasionally encountered. FISH results do not correlate with the presence of PPCs.
Light, temperature, and discharge control stream metabolism, but the response of gross primary production (GPP) and ecosystem respiration (ER) to seasonal variation in these physical drivers may ...differ in accordance with the types of human activities present in the catchment. Our study examined three mid-order streams in southern Ontario, Canada that differed in anthropogenic nutrient sources (i.e., sewage treatment plant effluent, sewage lagoon effluent, and agriculture), but had comparable light, temperature, and discharge regimes. For each stream, GPP and ER were estimated daily from June through November. Comparisons of paired daily metabolic rates revealed pairwise differences among all streams, with streams receiving sewage effluent having greater rates and variability of GPP and ER than the stream draining agricultural land. The two sewage influenced streams differed only in ER. Temporal patterns of GPP and ER were correlated for all streams throughout the study period and were most affected by seasonal variation in temperature, whereby effluent receiving streams responded more rapidly to increases in temperature. Our findings suggest that managers may need to balance effects of human activities with regional environmental constraints on stream metabolism to maintain and enhance the ecological condition and services of stream ecosystems.
Structural variants (SV) of the MYC gene region are common in multiple myeloma and influence disease progression. However, the prognostic significance of different MYC SVs in multiple myeloma has not ...been clearly established.
We conducted a retrospective study of multiple myeloma comparing MYC SV subtypes identified by next-generation sequencing (NGS) and FISH to MYC expression and disease survival using 140 cases from Mayo Clinic and 658 cases from the MMRF CoMMpass study.
MYC SVs were found in 41% of cases and were classified into nine subtypes. A correlation between the presence of a MYC SV and increased MYC expression was identified. Among the nine MYC subtypes, the non-immunoglobulin (non-Ig) insertion subtype was independently associated with improved outcomes, while the Ig insertion subtype, specifically involving the IgL gene partner, was independently associated with poorer outcomes compared with other MYC SV subtypes. Although the FISH methodology failed to detect approximately 70% of all MYC SVs, those detected by FISH were associated with elevated MYC gene expression and poor outcomes suggesting a different pathogenic role for FISH-detected MYC subtypes compared with other MYC subtypes.
Understanding the impact of different MYC SVs on disease outcome is necessary for the reliable interpretation of MYC SVs in multiple myeloma. NGS approaches should be considered as a replacement technique for a more comprehensive evaluation of the multiple myeloma clone.
Renal cell carcinoma with TFE3 rearrangement at Xp11.2 is a distinct subtype manifesting an indolent clinical course in children, with recent reports suggesting a more aggressive entity in adults. ...This subtype is morphologically heterogeneous and can be misclassified as clear cell or papillary renal cell carcinoma. TFE3 is also rearranged in alveolar soft part sarcoma. To aid in diagnosis, a break-apart strategy fluorescence in situ hybridization (FISH) probe set specific for TFE3 rearrangement and a reflex dual-color, single-fusion strategy probe set involving the most common TFE3 partner gene, ASPSCR1, were validated on formalin-fixed, paraffin-embedded tissues from nine alveolar soft part sarcoma, two suspected Xp11.2 renal cell carcinoma, and nine tumors in the differential diagnosis. The impact of tissue cut artifact was reduced through inclusion of a chromosome X centromere control probe. Analysis of the UOK-109 renal carcinoma cell line confirmed the break-apart TFE3 probe set can distinguish the subtle TFE3/NONO fusion-associated inversion of chromosome X. Subsequent extensive clinical experience was gained through analysis of 75 cases with an indication of Xp11.2 renal cell carcinoma (n=54), alveolar soft part sarcoma (n=13), perivascular epithelioid cell neoplasms (n=2), chordoma (n=1), or unspecified (n=5). We observed balanced and unbalanced chromosome X;17 translocations in both Xp11.2 renal cell carcinoma and alveolar soft part sarcoma, supporting a preference but not a necessity for the translocation to be balanced in the carcinoma and unbalanced in the sarcoma. We further demonstrate the unbalanced separation is atypical, with TFE3/ASPSCR1 fusion and loss of the derivative X chromosome but also an unanticipated normal X chromosome gain in both males and females. Other diverse sex chromosome copy number combinations were observed. Our TFE3 FISH assay is a useful adjunct to morphologic analysis of such challenging cases and will be applicable to assess the growing spectrum of TFE3-rearranged tumors.
Renal cell carcinoma (RCC) with chromosomal rearrangement of transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) at Xp11.2 is a distinct subtype that was initially described in ...children and has been reported to display an indolent course. Recent reports have identified RCC with TFE3 rearrangements in adults and have suggested a more aggressive course in this population. However, only a few studies have examined these tumors in a large series of consecutively treated adults. We screened 632 RCCs from patients consecutively treated by surgery at a single institution by fluorescence in situ hybridization to detect TFE3 rearrangements. We identified 6 RCCs with TFE3 rearrangement. Patient ages ranged from 25 to 78 years and included 4 women and 2 men. Tumors showed significant histologic variability. Comparison of the clinical and pathologic features between RCCs with TFE3 rearrangements and RCCs without TFE3 rearrangements showed no significant differences. Follow-up period for patients with TFE3-rearranged RCC ranged from 0.8 to 16.5 years, with 4 of 6 dying from the disease. Cancer-specific survival for patients with TFE3-rearranged RCC was significantly worse than for patients with TFE3-rearrangement-negative papillary-type RCC (P<0.001) but not different from that for TFE3-rearrangement-negative clear cell-type RCC. In conclusion, we present an assessment of TFE3 rearrangement status in a large series of adults consecutively treated by surgery for RCC. Our findings confirm that RCCs with TFE3 rearrangement account for only approximately 1% of adult RCCs. The results also suggest that adult RCC with TFE3 rearrangement may be a clinically aggressive tumor.
Objective This study aimed to determine whether 1p deletion defines a subset of cellular leiomyomata (CL), which is a hypercellular variant of uterine leiomyomata that may have delayed malignant ...potential, and to correlate this genetic change with clinical and pathologic characteristics including those present in uterine sarcomas. Study Design Available CL cases at the Mayo Clinic (n = 101) and variant cases reported in another article (n = 16) were identified. Each case with sufficient tissue that met histologic criteria for CL when reviewed by a single pathologist underwent interphase fluorescence in situ hybridization to determine the presence of 1p deletion. Clinical characteristics of women with confirmed CL were compared on the basis of 1p deletion status using univariate analysis. Results Of the Mayo Clinic cohort of histologically confirmed CL, 23% had deletion of 1p. Women with this subset of CL, when compared to those without 1p deletion, were more likely to be postmenopausal ( P = .049) and their uteri tended to be heavier ( P = .039) with a larger dominant leiomyoma ( P = .030). The pathologic features associated with 1p deletion were high cellularity ( P = .036) and hyaline necrosis ( P = .047), which remained significant after inclusion of the CL cases from a previously published series. Conclusion Deletion of 1p occurs in approximately one-quarter of CL cases. This genetic alteration is potentially associated with clinicopathologic features that are present in uterine sarcomas, which suggests a distinct clinical entity that may have malignant potential. Our findings are particularly pertinent considering the increased preference for uterine-sparing options in leiomyoma treatment, suggesting assessment of 1p deletion status in CL may influence clinical surveillance decisions.
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