Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value

An, Gang; Xu, Yan; Shi, Lihui; Zhang, Shizhen; Deng, Shuhui; Xie, Zhenqing; Sui, Weiwei; Zhan, Fenghuang; Qiu, Lugui

doi:10.3324/haematol.2013.088211

Cited by 105 publications

(114 citation statements)

References 24 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…Multiple studies have shown that chromosome 1q21 gains are associated with an inferior outcome in multiple myeloma (9,10,31), which has been supported by several basic researches (32,33). As in previous studies, we found that the percentage of myeloma cells carrying a 1q21 gains within total myeloma cells of a given patient increased with disease progression, indicating that 1q21 was a "progression-related" aberration.…”

Section: Discussionsupporting

confidence: 71%

The Impact of Clone Size on the Prognostic Value of Chromosome Aberrations by Fluorescence In Situ Hybridization in Multiple Myeloma

Tai

et al. 2015

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Accumulating evidence indicates that intratumor heterogeneity is prevalent in multiple myeloma and that a collection of multiple, genetically distinct subclones are present within the myeloma cell population. It is not clear whether the size of clonal myeloma populations harboring unique cytogenetic abnormalities carry any additional prognostic value.Experimental Design: We analyzed the prognostic impact of cytogenetic aberrations by fluorescence in situ hybridization at different cutoff values in a cohort of 333 patients with newly diagnosed myeloma and 92 patients with relapsed myeloma.Results: We found that nearly all IgH-related arrangements were observed in a large majority of the purified plasma cells; however, 13q deletion, 17p deletion, and 1q21 amplification appeared in different percentages within the malignant plasma cell population. Based on the size of subclones carrying these cytogenetic aberrations, the patients were divided into four groups: 0%-10%, 10.5%-20%, 20.5%-50%, and >50%. Receiver-operating characteristics analysis was applied to determine the optimal cutoff value with the greatest differential survival and showed that the most powerful clone sizes were 10% for 13q deletion, 50% for 17p deletion, and 20% for 1q21 gains, which provided the best possible cutoffs for predicting poor outcomes.Conclusions: Our study indicated that the impact of clone size on prognostic value varies between specific genetic abnormalities. Prognostic value was observed for even a subgroup of plasma cells harboring the cytogenetic aberration of 13q deletion and 1q21 gains; however, 17p deletion displayed the most powerful cutoff for predicting survival only if the predominant clones harbored the abnormality.

show abstract

Section: Discussionsupporting

confidence: 71%

The Impact of Clone Size on the Prognostic Value of Chromosome Aberrations by Fluorescence In Situ Hybridization in Multiple Myeloma

Tai

et al. 2015

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Furthermore, patients with down-regulated miR-19a expression had a significantly shortened PFS (11.0 months, p=0.002) and shortened OS (28.1 months, p=0.020) than patients with increased miR-19a expression (Figure 4A). Interestingly, a positive correlation was drawn between miR-19a and 1q21 amplification (r=0.228, p=0.023).Patients exhibiting the 1q21 amplification correlation had a poorer clinical outcome, which is consistent with previous studies 23 . Therefore, we then analyzed the survival of patients with miR-19a in the absence of 1q21 amplification and found that the median PFS among these cases were 12.5 months (p=0.026).…”

Section: Resultssupporting

confidence: 89%

“…All patients signed an informed consent form approved by the Institutional local ethics committee. For 103 newly diagnosed MM patients, bone marrow plasma cells (BMPC) were obtained for routine fluorescence in situ hybridization analysis (FISH), specifically for del(13q14), del(17p),t(11;14), t(4;14), t(14;16) and 1q21 amplification, as described previously 23 .…”

Section: Methodsmentioning

confidence: 99%

Low serum miR‐19a expression as a novel poor prognostic indicator in multiple myeloma

Hao

Zang

Wendlandt

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

Multiple myeloma (MM) is the second most common hematologic malignancy characterized by the clonal expansion of plasma cells. Despite continuing advances, novel biomarkers are needed for diagnosis and prognosis of MM. In this study we characterized the diagnostic and prognostic potential of circulating miRNAs in MM. Serum miRNA levels were analyzed in 108 newly diagnosed symptomatic MM patients and 56 healthy donors (HD). Our analysis identified ninety-five dysregulated miRNAs in newly diagnosed MM patients. Of the ninety-five dysregulated miRNAs, dysregulation of miR-19a, miR-92a, miR-214-3p, miR-135b-5p, miR-4254, miR-3658 and miR-33b were confirmed by RT-qPCR. Receiver operating characteristic analysis revealed that a combination of miR-19a and miR-4254 can distinguish MM from HD with a sensitivity of 91.7% and specificity of 90.5%. Decreased expression of miR-19a was positively correlated with international staging system advancement, del(13q14) and 1q21 amplification. Furthermore, down-regulation of miR-19a resulted in significantly decreased progression free and overall survival. Our analysis indicated that the poor prognostic correlation of miR-19a expression was independent of genetic abnormalities in MM. Multivariate analysis revealed that miR-19a was a significant predictor of shortened PFS and OS. Interestingly, although miR-19a levels portend a poor prognosis, patients with low miR-19a levels had an improved response to bortezomib compared to patients with high miR-19a profile. Patients with down-regulated miR-19a experienced a significantly extended survival upon bortezomib based therapy. These data demonstrate that the expression patterns of serum microRNAs are altered in MM and miR-19a levels are a valuable prognostic marker to identify high-risk MM.

show abstract

“…Similar to our previous observations (20), the majority of cases with 16p13.3 gain harbored a single extra copy. Single copy gains of loci or entire chromosome are known recurrent events in other types of cancer that effectively contribute to tumor phenotypes (27)(28)(29)(30). A few cases harbored more than a single copy gain, and they were more prevalent in the pT3-stage tumors.…”

Section: Discussionmentioning

confidence: 99%

Genomic Gain of 16p13.3 in Prostate Cancer Predicts Poor Clinical Outcome after Surgical Intervention

Bramhecha

Guérard

Rouzbeh

et al. 2018

Molecular Cancer Research

View full text Add to dashboard Cite

Identifying tumors with high metastatic potential is key to improving the clinical management of prostate cancer. Recently, we characterized a chromosome 16p13.3 gain frequently observed in prostate cancer metastases and now demonstrate the prognostic value of this genomic alteration in surgically treated prostate cancer. Dual-color FISH was used to detect 16p13.3 gain on a human tissue microarray representing 304 primary radical prostatectomy (RP) cases with clinical followup data. The results were validated in an external dataset. The 16p13.3 gain was detected in 42% (113/267) of the specimens scorable by FISH and was significantly associated with clinicopathologic features of aggressive prostate cancer, including high preoperative PSA (P ¼ 0.03) levels, high Gleason score (GS, P < 0.0001), advanced pathologic tumor stage (P < 0.0001), and positive surgical margins (P ¼ 0.009). The 16p13.3 gain predicted biochemical recurrence (BCR) in the overall cohort (log-rank P ¼ 0.0005), and in subsets of patients with PSA 10 or GS 7 (log-rank P ¼ 0.02 and P ¼ 0.006, respectively). Moreover, combining the 16p13.3 gain status with standard prognostic markers improved BCR risk stratification and identified a subgroup of patients with high probability of recurrence. The 16p13.3 gain status was also associated with an increased risk of developing distant metastases (log-rank P ¼ 0.03) further substantiating its role in prostate cancer progression.Implications: This study demonstrates the prognostic significance of the 16p13.3 genomic gain in primary prostate tumors, suggesting potential utility in the clinical management of the disease by identifying patients at high risk of recurrence who may benefit from adjuvant therapies.

show abstract

Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value

Cited by 105 publications

References 24 publications

The Impact of Clone Size on the Prognostic Value of Chromosome Aberrations by Fluorescence In Situ Hybridization in Multiple Myeloma

The Impact of Clone Size on the Prognostic Value of Chromosome Aberrations by Fluorescence In Situ Hybridization in Multiple Myeloma

Low serum miR‐19a expression as a novel poor prognostic indicator in multiple myeloma

Genomic Gain of 16p13.3 in Prostate Cancer Predicts Poor Clinical Outcome after Surgical Intervention

Contact Info

Product

Resources

About