Current and Proposed Molecular Diagnostics in a Genitourinary Service Line Laboratory at a Tertiary Clinical Institution

Udager, Aaron M.; Alva, Ajjai; Mehra, Rohit

doi:10.1097/ppo.0000000000000017

Cited by 17 publications

(13 citation statements)

References 84 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The recurrent chromosomal loss we observed by exome sequencing supports a recent study by Peckova et al (16) that reported similar recurrent chromosomal losses using array CGH and FISH strategies. Importantly none of the samples in this cohort with pure MTSCC histology displayed chromosomes 7 and 17 gains, commonly noted as gains in type I papillary RCC(17). The recent TCGA papillary RCC (KIRP) study reported Hippo pathway mutations ( NF2 and SAV1 ) in 4% of the samples and used CNV to classify tumors into 3 groups such as genome stable, unstable and chromosome 7/17 gains(2).…”

Section: Resultsmentioning

confidence: 87%

Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

et al. 2016

Self Cite

View full text Add to dashboard Cite

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma with distinctive morphologic and cytogenetic features. Here we carry out whole exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n=22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSGs) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes while other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to bi-allelic alterations in these TSGs. As a read-out of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. Taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation.

show abstract

Section: Resultsmentioning

confidence: 87%

Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…HER2 expression can be determined using different methods, such as IHC, enzyme-linked immunosorbent assay, fluorescent (FISH), and PCR [40]; both IHC and ISH are considered among current molecular diagnostics tools in a Genitourinary Service Line Laboratory at a Tertiary Clinical Institution [41].…”

Section: Issues In Her2 Assessment Methodsmentioning

confidence: 99%

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

et al. 2018

View full text Add to dashboard Cite

Although human epidermal growth factor receptor 2 (HER2) plays a prognostic and predictive role in breast and gastric cancer, its function in bladder cancer (BC) is still controversial. A comprehensive review of the literature has been carried out. An electronic search of databases from PubMed, Scopus, Google Scholar was implemented. The search terms were: “BC,” “bladder carcinoma,” “bladder neoplasm,” “human epidermal growth factor 2,” “HER2,” “HER-2,” “c-erbB-2,” “c-erbB2,” “erbB-2,” “erbB2,” “neu,” “marker,” “biomarker,” and “prognosis”. Results of the review consented to (a) summarize the available data on HER2 a predictor of recurrence and/or progression free survival on univariate and multivariate analysis, (b) explore the related issues in assessing HER2 status on these tumor samples, since they may severely impair its predictive function, and (c) report the state-of-the art of HER2 as a putative therapeutic target in BC and especially non-muscle invasive BC. HER2 stands out for being a prognostic factor as well as a therapeutic target in various cancers. Data from the literature concerning its use in BC provide conflicting results, probably due to the inherent complexity of BC biology. Efforts should be made to establish a suitable tumor-specific scoring system, and to assess single drugs’ efficacy in well-designed clinical trials.

show abstract

“…Numerous long noncoding RNAs (lncRNAs) have recently emerged as targets for clinical translation [1,2]. We previously identified 121 novel, differentially expressed prostate cancer (PCa) lncRNAs, including SChLAP1, which is overexpressed in a subset of tumors and associated with more aggressive disease [3–5].…”

mentioning

confidence: 99%

Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer

et al. 2016

Self Cite

View full text Add to dashboard Cite

The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression according to in situ hybridization (ISH) independently predicts biochemical recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0–400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score ≥100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1–4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression.

show abstract

Current and Proposed Molecular Diagnostics in a Genitourinary Service Line Laboratory at a Tertiary Clinical Institution

Cited by 17 publications

References 84 publications

Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer

Contact Info

Product

Resources

About