Targeted resequencing of 9p in acute lymphoblastic leukemia yields concordant results with array CGH and reveals novel genomic alterations

Sarhadi, Virinder; Lahti, Leo; Scheinin, Ilari; Tyybäkinoja, Anne; Savola, Suvi; Usvasalo, Anu; Räty, Riikka; Elonen, Erkki; Ellonen, Pekka; Saarinen‐Pihkala, Ulla M.; Knuutila, Sakari

doi:10.1016/j.ygeno.2013.01.001

Cited by 18 publications

(23 citation statements)

References 29 publications

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“…Next generation sequencing (NGS) provides an effective tool to study the genetic complexity of malignant tumors. NGS methods enable simultaneous variation and mutation screening of many different genes or even whole genomes in many samples using a single test (Ansorge, ; Metzker, ; Gullapalli et al ; Sarhadi et al, ; Tuononen et al, a,b).…”

Section: Introductionmentioning

confidence: 99%

Mutated Ephrin Receptor Genes in Non‐Small Cell Lung Carcinoma and Their Occurrence with Driver Mutations—Targeted Resequencing Study on Formalin‐Fixed, Paraffin‐Embedded Tumor Material of 81 Patients

Mäki-Nevala

Sarhadi

Tuononen

et al. 2013

Genes Chromosomes & Cancer

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Non-small cell lung carcinoma (NSCLC) is the most common subtype of lung cancer. The oncogenic potential of receptor tyrosine kinases (RTKs) is widely known and they are potential targets for tailored therapy. Ephrin receptors (Ephs) form the largest group of RTKs. Nevertheless, Ephs are not widely studied in NSCLC so far. The aim of our study was to investigate novel mutations of Eph genes (EPHA1-8, EPHB1-4, EPHB6) and their association with clinically relevant mutations in BRAF, EML4-ALK, EGFR, INSR, KDR, KRAS, MET, PDGFRA, PDGFRB, PIK3, PTEN, RET, and TP53 in NSCLC patients. Targeted resequencing was conducted on 81 formalin-fixed, paraffin-embedded NSCLC tumor specimens. We analyzed missense and nonsense mutations harbored in the coding regions of the selected genes. We found 18 novel mutations of Ephs in 20% (16 of 81) of the patients. Nearly half of these mutations occurred in the protein kinase domain. The mutations were not mutually exclusive with other clinically relevant mutations. Our study shows that Ephs are frequently mutated in NSCLC patients, and occur together with other known mutations relevant to the pathogenicity of NSCLC.

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Section: Introductionmentioning

confidence: 99%

Mutated Ephrin Receptor Genes in Non‐Small Cell Lung Carcinoma and Their Occurrence with Driver Mutations—Targeted Resequencing Study on Formalin‐Fixed, Paraffin‐Embedded Tumor Material of 81 Patients

Mäki-Nevala

Sarhadi

Tuononen

et al. 2013

Genes Chromosomes & Cancer

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“…For ALL, patients examined previously by aCGH (Usvasalo et al, ) and those for whom enough DNA was available were selected. The NGS results from these patients have been described earlier (Sarhadi et al, ) and are included in the present study. With respect to lung cancer, both small cell and non‐small‐cell lung cancer patients studied by aCGH (conventional CGH for five LC patients) were selected (Nymark et al, ).…”

Section: Methodsmentioning

confidence: 93%

“…Custom designed baits were obtained from NimbleGen (Roche NimbleGen, Madison, WI, USA). A total of 2,358 target regions, consisting of 191 protein coding and miRNA genes were covered in the capture as described earlier (Sarhadi et al, ). On average, 93% of the target had more than 20× coverage.…”

Section: Methodsmentioning

confidence: 99%

Copy number alterations and neoplasia‐specific mutations in MELK, PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias

Sarhadi

Lahti

Ilari

et al. 2014

Genes Chromosomes & Cancer

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Genetic alterations affecting 9p are commonly present in many cancer types and many cancer-related genes are located in this chromosomal region. We sequenced all of the genes located in a 32Mb region of 9p by targeted next generation sequencing (NGS) in 96 patients with different cancer types, including acute lymphoblastic leukemia, bone malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, fibrosarcoma, Ewing's sarcoma, and lung carcinoma. Copy number alterations (CNA), and mutations were studied from the NGS data. We detected a deletion at the CDKN2A locus as being the most frequent genetic alteration in all cancer types. In addition to this locus, NGS also identified other small regions of copy number loss and gain. However, different cancer types did not reveal any statistically significant differences with regard to CNA frequency or type. Of the 191 genes within the target region, two novel recurrent mutations were found in the MELK and PDCD1LG2 genes. The most commonly mutated gene in sarcomas was TLN1 (8%) and PAX5 in ALL (9%). Mutations in PAX5, and RUSC2, were seen exclusively in ALL patients and those in KIAA1432, CA9, TLN1, and MELK only in sarcomas (MFH, FS, EFT). Thus using targeted NGS of the 9p region, in addition to commonly deleted CDKN2A locus, we were able to identify a number of small deletions and gains, as well as novel recurrent mutations in different cancer types. © 2014 Wiley Periodicals, Inc.

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“…Methods for NGS, aCGH, FISH, RT-PCR, and IHC appear in the original articles [1-3]. Our NGS method was based on targeted resequencing.…”

Section: Methodsmentioning

confidence: 99%

“…This presentation based on our three papers [1-3] in press illustrates the feasibility, even superiority of NGS for biomarker analysis in human neoplasias.…”

Section: Introductionmentioning

confidence: 92%

Biomarker analysis in human neoplasias: superior next-generation sequencing on frozen bone marrow cells and on formalin-fixed, paraffin-embedded tumor tissues

Targeted resequencing of 9p in acute lymphoblastic leukemia yields concordant results with array CGH and reveals novel genomic alterations

Cited by 18 publications

References 29 publications

Mutated Ephrin Receptor Genes in Non‐Small Cell Lung Carcinoma and Their Occurrence with Driver Mutations—Targeted Resequencing Study on Formalin‐Fixed, Paraffin‐Embedded Tumor Material of 81 Patients

Mutated Ephrin Receptor Genes in Non‐Small Cell Lung Carcinoma and Their Occurrence with Driver Mutations—Targeted Resequencing Study on Formalin‐Fixed, Paraffin‐Embedded Tumor Material of 81 Patients

Copy number alterations and neoplasia‐specific mutations in MELK, PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias

Biomarker analysis in human neoplasias: superior next-generation sequencing on frozen bone marrow cells and on formalin-fixed, paraffin-embedded tumor tissues

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