Next-Generation Sequencing–Based Assessment of JAK2, PD-L1, and PD-L2 Copy Number Alterations at 9p24.1 in Breast Cancer

Gupta, Sounak; Vanderbilt, Chad; Cotzia, Paolo; Arias‐Stella, Javier; Chang, Jason C.; Zehir, Ahmet; Benayed, Ryma; Nafa, Khedoujia; Razavi, Pedram; Hyman, David M.; Baselga, José; Berger, Michael F.; Ladanyi, Marc; Arcila, Maria E.; Ross, Dara S.

doi:10.1016/j.jmoldx.2018.10.006

Cited by 22 publications

(16 citation statements)

References 40 publications

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“…However, in our study, deletion of 9p24.1 was associated with shorter OS (Figure 3E, P=0.0376). In a recent study, high frequency 9p24.1 deletion occurred in the post chemotherapy setting but the significance is unclear, requiring further studies (15). Additionally, we found 16p11.2 amplification in 5 (13.2%) patients (Figure 3F, P=0.0066).…”

Section: Aberrations In Somatic Copy Number Alterationmentioning

confidence: 46%

Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer

Zhu

Wang

et al. 2020

Ann Transl Med

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Background: Gastric cancer (GC) is a heterogeneous disease, and is a leading cause of cancer deaths in Eastern Asia. Genomic analysis, such as whole-exome sequencing (WES), can help identify key genetic alterations leading to the malignancy and diversity of GC, and may help identify new drug targets.Methods: We identified genomic alterations in a cohort of 38 GC patients, including 26 metastatic and 12 non-metastatic patients. We analyzed the association between novel gene mutations and copy number variations (CNVs) with tumor metastasis and patient survival.Results: A number of significantly mutated genes in somatic and germline cells were identified. Among them, ATAD3B somatic mutation, a potential biomarker of immunotherapy in stomach cancers, was associated with better patient survival (P=0.0939) and metastasis (P=0.074). POLE germline variation was correlated with shorter overall survival (OS; P=0.0100). Novel CNVs were also identified and can potentially be used as biomarkers. These included 9p24.1 deletion (P=0.0376) and 16p11.2 amplification (P=0.0066), which were both associated with shorter OS. CNVs of several genes including MMP9, PTPN1, and SS18L1 were found to be significantly related to metastasis (P<0.05). Conclusions:We characterized the mutational landscape of 38 GC patients and discovered several potential new predictive markers of survival and metastasis in GC.

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Section: Aberrations In Somatic Copy Number Alterationmentioning

confidence: 46%

Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer

Zhu

Wang

et al. 2020

Ann Transl Med

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“…For example, in mice PD-L1, but not PD-L2 associated with the development of autoimmune diabetes [17]. The comparison of PD-L1 and PD-L2 functions is still under investigation and, to date, few studies have examined the correlations of different types of immune cell infiltrates with the prognostic and therapeutic significance of PD-L2 in human cancers [18,19,20,21,22]. A detailed knowledge of PD-L regulation should help identify patients who will not respond to PD-1 blockade therapy.…”

Section: Pd-1/pd-l1 Immune Checkpoint In Chlmentioning

confidence: 99%

Classical Hodgkin’s Lymphoma in the Era of Immune Checkpoint Inhibition

Caggiari

Repetto

et al. 2019

JCM

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: The ligation of programmed cell death 1 (PD-1) with programmed cell death ligand PD-L activates the immune checkpoint leading to T-cell dysfunction, exhaustion, and tolerance, especially in Hodgkin lymphoma (HL) where the PD-L/ Janus kinase (Jak) signaling was frequently found altered. Anti-PD-1 or anti-PD-L1 monoclonal antibodies can reverse this immune checkpoint, releasing the brake on T-cell responses. The characterization of the mechanisms regulating both the expression of PD-1 and PD-L and their function(s) in HL is ongoing. We provide in this review the recent findings focused on this aim with special attention on the major research topics, such as adverse events and resistance to PD-1–PD-L1 inhibitor treatment, together with a part about angiogenesis, extracellular vesicles, and microbiome in HL pathogenesis.

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“…It is because of this reason for particularly choosing this mutation for study . Recent studies suggest that an amplification of JAK2 gene on somatic chromosome 9p24.1 region in patients with TNBC . Ruxolitinib is an orally available JAK2 inhibitor that can be useful in this subgroup of patients .…”

Section: Status Of Healthy Controlsmentioning

confidence: 99%

Detection of JAK2 gene mutation in Pakistani women with triple‐negative breast cancer

et al. 2019

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Triple-negative breast cancers (TNBCs) are defined as lack of expression of estrogen, progesterone, and Her2neu receptors by immunohistochemistry. 1 This subgroup has an aggressive clinical behavior. 2 JAK2 (V617F) exon 14 is a most probable mutation in occurring in pseudo kinase domain with loss of intrinsic auto inhibitory activity and can result in malignant transformation and uncontrolled proliferation leading to TNBC. It is because of this reason for particularly choosing this mutation for study. 3 Recent studies suggest that an amplification of JAK2 gene on somatic chromosome 9p24.1 region in patients with TNBC. 4 Ruxolitinib is an orally available JAK2 inhibitor that can be useful in this subgroup of patients. 5 A total of two hundred and fifty consecutively selected premenopausal, pretreatment female patients at CMH Lahore between 25 and 60 years diagnosed during past 2 years (Jan 2017Jan 2019) as triple-negative breast cancer (estrogen, progesterone, and Her 2 neu negative) in stage M1 on immuno histochemistry examination of breast tissue were included in the study. The presence of myeloproliferative neoplasms (MPN) was ruled out in all patients. Informed consent was obtained from all patients involved in the study. All the blood samples were taken before the start of treatment in TNBC cases. A cohort of age-matched consecutively selected female volunteers (n = 100) was included as unpaid healthy controls after written informed consent. Permission for the study was taken from hospital ethical committee. Real-time polymerase chain reaction was done on all the samples. Real-time polymerase chain reaction was used for amplification of DNA and was carried out in thermal cycler Rotor-Gene-Q (Corbett Research) having quality of rapidly heating and cooling of samples. The results of RT-PCR were recorded as cycle threshold (C t ), and C t < 20 was taken as positive and rest was taken as negative. Positive and negative control DNA samples for JAK2 V617F mutations were included in all batches. Positive samples were further tested for additional mutations that affect signaling pathway notably JAK2 exon12, STAT, KRAS, NRAS, CBL1, PTPN11, RAF, MAP, MYC, and PI3K mutations by Sanger sequencing. JAK2 exon 14-positive DNA of an age-matched MPN negative TNBC patient was taken as positive control while exon 14-negative DNA of an age-matched MPN negative TNBC patient was taken as negative control for PCR. To check the robustness of JAK2 V617F exon 14 mutation assays, quantitative results performed were found to be reliable across all mutation loads with moderate variability at low allele burden (0.1 and 1%; CV = 0.45 and 0.76, respectively). The percentage of samples correctly identified as positive and negative for the JAK2 V617F exon 14 mutation in both groups was calculated. The kappa value (k) was used to determine the level of agreement between each alternative assay and the PCR sequencing. All healthy controls (n = 100) were negative (DNA) for JAK2 V617F exon 14 mutation by real-time PCR. A total of twenty-five (n = ...

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Next-Generation Sequencing–Based Assessment of JAK2, PD-L1, and PD-L2 Copy Number Alterations at 9p24.1 in Breast Cancer

Cited by 22 publications

References 40 publications

Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer

Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer

Classical Hodgkin’s Lymphoma in the Era of Immune Checkpoint Inhibition

Detection of JAK2 gene mutation in Pakistani women with triple‐negative breast cancer

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