Novel ALK fusion partners in lung cancer

Iyevleva, Aglaya G.; Raskin, Grigory A.; Tiurin, Vladislav I.; Sokolenko, Anna P.; Mitiushkina, Natalia V.; Aleksakhina, Svetlana N.; Гарифуллина, А Р; Strelkova, Tatiana N.; Merkulov, Valery O.; Ivantsov, Alexandr O.; Kuligina, Ekatherina Sh.; Pozharisski, Kazymir M.; Togo, Alexandr V.; Imyanitov, Evgeny N.

doi:10.1016/j.canlet.2015.03.028

Cited by 75 publications

(62 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, RT‐PCR analysis utilizes the same technical platform as other kinds of molecular NSCLC diagnosis, for example EGFR testing. Finally, a number of commercial RT‐PCR kits for detection of ALK rearrangements have been developed recently, including: the ALK RGQ RT‐PCR Kit (Qiagen, Valencia, CA, USA); the EML4‐ALK Fusion Gene Detection Kit (Amoy Diagnostics, Xiamen, China); and EML4 ALK Gene Fusion, PCR (Quest Diagnostics, Secaucus, NJ, USA) . However, there are some disadvantages of this platform.…”

Section: Alk Rearrangement Detection Methods In Nsclc Patientsmentioning

confidence: 99%

“…Rearrangements of the ALK gene with partner genes other than EML4 have been described, namely, KIF5B , KLC1 , TFG , TPR , HIP1 , STRN , DCTN1 , SQSTM1 , NPM1 , BCL11A , and BIRC6 (Table ) . Targeted therapeutic agents, including the TKI crizotinib, have shown clinical efficacy in treating NSCLC patients harboring EML4‐ALK gene fusion .…”

Section: Alk Rearrangement In Non‐small Cell Lung Cancer (Nsclc)mentioning

confidence: 99%

See 1 more Smart Citation

ALK‐rearrangement in non‐small‐cell lung cancer (NSCLC)

et al. 2018

View full text Add to dashboard Cite

The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large‐cell lymphoma. Since then, ALK has been associated with other types of cancers, including non‐small‐cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK‐rearrangement (ALK‐R), and the ALK‐tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.

show abstract

Section: Alk Rearrangement Detection Methods In Nsclc Patientsmentioning

confidence: 99%

Section: Alk Rearrangement In Non‐small Cell Lung Cancer (Nsclc)mentioning

confidence: 99%

ALK‐rearrangement in non‐small‐cell lung cancer (NSCLC)

et al. 2018

View full text Add to dashboard Cite

show abstract

“…We and others reported PCR tests, which utilize cDNA as a template and measure the amounts of 5′‐ and 3′‐end specific fragments of the involved tyrosine kinase 14‐16 . If the rearrangement occurs, the kinase domain of the involved gene is translocated to a highly expressed partner; therefore, the 3′‐end of the transcript is overrepresented as compared with the 5′‐end.…”

Section: Introductionmentioning

confidence: 99%

Gene rearrangements in consecutive series of pediatric inflammatory myofibroblastic tumors

Preobrazhenskaya

Iyevleva

Suleymanova

et al. 2020

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

Background Inflammatory myofibroblastic tumors (IMTs) are exceptionally rare neoplasms, which are often driven by rearranged tyrosine kinases. Methods This study considered 33 consecutive patients with IMT (median age, 6.6; age range, 0.6‐15.8 years). RNA and cDNA were successfully obtained in 29 cases. The molecular analysis included sequential tests for 5′/3′‐end unbalanced gene expression, variant‐specific PCR, and next‐generation sequencing (NGS). Results 5′/3′‐end unbalanced ALK expression was revealed in 15/29 (52%) IMTs. Strikingly, all these tumors demonstrated high amount of ALK protein detected by immunohistochemistry. Variant‐specific PCR was capable of identifying the type of ALK rearrangement in 11/15 IMTs with 5′/3′‐end unbalanced ALK expression. The remaining four tumors were analyzed by NGS; two known and two novel (CLTC‐ins6del84‐ALK and EEF1G‐ALK) ALK rearrangements were detected. Five IMTs demonstrated 5′/3′‐end unbalanced ROS1 expression, and all these tumors carried TFG‐ROS1 fusion. Nine tumors, which were negative for 5′/3′‐end unbalanced ALK/ROS1 expression, were subjected to further analysis. Variant‐specific PCR revealed two additional tumors with gene rearrangements (TFG‐ROS1 and ETV6‐NTRK3). The remaining seven IMTs were tested by NGS; single instances of TFG‐ROS1 and novel SRF‐PDGFRb translocations were detected. Conclusions Twenty‐four of 29 IMTs (83%) were shown to have druggable rearrangements involving tyrosine kinases, 20 of these 24 gene fusions were detectable by simple and inexpensive PCR assay, which is based on the detection 5′/3′‐end unbalanced gene expression.

show abstract

“…We aimed to detect the most common ALK fusion proteins simultaneously. However, it was difficult to cover all the hybrid variants since new discoveries are still emerging [12, 13]. Thus, there could have been some false negative results in the detailed subtype analysis compared to the FISH analysis.…”

Section: Discussionmentioning

confidence: 99%

Detection of ALK rearrangements in lung cancer patients using a homebrew PCR assay

Chang

Liu

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Lung cancer patients with anaplastic lymphoma kinase (ALK) rearrangements are candidates for targeted therapeutics. However, patients must be tested with a companion diagnostic assay to realize their ALK rearrangement status. We analyzed the publicly available E-GEOD-31210 microarray dataset and identified a non-coding RNA, sweyjawbu, which is strongly associated with ALK rearrangements. We validated these results using quantitative real-time PCR in an independent cohort consisting of 4 cell lines and 83 clinical samples. We could differentiate between ALK rearrangement-positive and -negative lung cancer samples by comparing sweyjawbu expression. Additionally, ALK rearrangement status was determined by comparing the expression of the 5′ and 3′ regions of the ALK transcript or by detecting known ALK hybrid subtypes. Thus, using our homebrew PCR assay, we were able to accurately detect ALK rearrangements, which could be used for diagnostic screening of lung cancer patients. The prototype could potentially be transferred to an automatic multiplex PCR platform (FilmArray) to differentiate between ALK rearrangement-positive and -negative patients in point-of-care settings.

show abstract

Novel ALK fusion partners in lung cancer

Cited by 75 publications

References 32 publications

ALK‐rearrangement in non‐small‐cell lung cancer (NSCLC)

ALK‐rearrangement in non‐small‐cell lung cancer (NSCLC)

Gene rearrangements in consecutive series of pediatric inflammatory myofibroblastic tumors

Detection of ALK rearrangements in lung cancer patients using a homebrew PCR assay

Contact Info

Product

Resources

About