Concomitant EGFR mutation and ALK rearrangement in lung adenocarcinoma is more frequent than expected: Report of a case and review of the literature with demonstration of genes alteration into the same tumor cells

Baldi, Licia; Mengoli, Maria Cecilia; Bisagni, Alessandra; Banzi, M.; Boni, C.; Rossi, Giulio

doi:10.1016/j.lungcan.2014.09.011

Cited by 58 publications

(51 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Knockdown of CHCHD2 was accompanied by reduced expression of ALK; however, to the best of our knowledge, wild-type ALK, which is known to function in brain development and neural function, has not been implicated as an oncogenic driver. Interestingly, recent observations of concomitant EGFR mutation and ALK gene rearrangement has suggested that coordinated activation of the signaling networks of EGFR and ALK may be important in lung ADC (50). Although not tested in this study, our results suggest that coamplification of CHCHD2 and EGFR may be linked to ALK.…”

Section: Discussionmentioning

confidence: 45%

CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration

Wei

Vellanki

Coyaud

et al. 2015

Molecular Cancer Research

View full text Add to dashboard Cite

Coiled-coil-helix-coiled-coil-helix domain-containing 2, a mitochondrial protein, encoded by CHCHD2 is located at chromosome 7p11.2 and proximal to the EGFR gene. Here, bioinformatic analyses revealed that CHCHD2 is consistently coamplified with EGFR in non-small cell lung carcinoma (NSCLC). In addition, CHCHD2 and EGFR protein expression levels were positively correlated and upregulated relative to normal lung in NSCLC tumor-derived xenografts. Knockdown of CHCHD2 expression in NSCLC cells attenuated cell proliferation, migration, and mitochondrial respiration. CHCHD2 protein-protein interactions were assessed by the complementary approaches of affinity purification mass spectrometry and in vivo proximity ligation. The CHCHD2 interactome includes the apparent hub proteins C1QBP (a mitochondrial protein) and YBX1 (an oncogenic transcription factor), and an overlapping set of hub-associated proteins implicated in cell regulation.Implications: CHCHD2 influences mitochondrial and nuclear functions and contributes to the cancer phenotype associated with 7p11.2 amplification in NSCLC. Mol Cancer Res; 13(7); 1119-29. Ó2015 AACR.

show abstract

Section: Discussionmentioning

confidence: 45%

CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration

Wei

Vellanki

Coyaud

et al. 2015

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…Although this strategy is prudent in that more non-small cell lung carcinoma cases will possess an EGFR mutation rather than an ALK translocation/amplification, it has been shown that these two events are not completely mutually exclusive. 6,7 This algorithm holds the risk of (1) potentially missing a rare case harboring both an EGFR mutation and ALK translocation; (2) exhausting the small amount of testing material from small biopsies and cytology specimens, rendering the possibility of the ALK FISH assay not being performed; and (3) increasing the overall turnaround time for molecular result reporting.…”

Section: Commentmentioning

confidence: 99%

Clinical Validation of a Novel Commercial Reverse Transcription–Quantitative Polymerase Chain Reaction Screening Assay for Detection of ALK Translocations and Amplifications in Non–Small Cell Lung Carcinomas

Liu

Pepper

Hendrickson

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.-EGFR mutations and anaplastic lymphoma kinase (ALK) translocations have significant biologic and therapeutic implications in lung cancers, particularly lung adenocarcinomas. ALK translocations are less frequent compared with EGFR mutations; interestingly, these two abnormalities are most commonly mutually exclusive. The 2013 College of American Pathologists/Association for Molecular Pathology/International Association for the Study of Lung Cancer molecular testing guideline for lung cancers recommend a testing algorithm in which detection of ALK translocations using fluorescence in situ hybridization (FISH) is to be performed following testing for EGFR mutations. Such an algorithm is cost-effective but potentially slows down turnaround time; and as a secondary test, ALK FISH assay may not be completed because it requires the use of additional tissue, and the small biopsies or cytology specimens may have been exhausted in the extraction of nucleic acid for EGFR mutation screening.Objective.-To provide efficient testing of both EGFR and ALK genetic alterations in small biopsies and cytology specimens.Design.-We validated a highly sensitive ALK reverse transcription-quantitative polymerase chain reaction (RTqPCR) assay as a screening tool for ALK translocations and amplifications.Results.-We performed a retrospective review of cases previously tested by FISH and found that all FISH ALK translocation-positive specimens were RT-qPCR positive, and all FISH ALK translocation-negative cases were RTqPCR negative (the sensitivity and specificity of the ALK RT-qPCR assay were 100%).Conclusion.-This assay allows rapid identification of ALK alterations, can be performed in conjunction with EGFR testing, and does not require use of valuable additional tumor tissue.

show abstract

“…Coexistent genetic alterations in cancer-driving genes, i.e., KRAS mutations, PTEN loss and BIM polymorphisms were identified to be associated with primary resistance for EGFR-TKIs treatment [13–14]. But, most studies focused on concurrent ALK and EGFR mutations [15–16]. Other genes such as PIK3CA and HER2 were not well reported.…”

Section: Introductionmentioning

confidence: 99%

Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in Chinese patients with non-small cell lung cancer

Liu

Chen

2017

Oncotarget

View full text Add to dashboard Cite

PurposeWe investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment.MethodsThree hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR. Progression-free survival and overall survival with EGFR-TKIs treatment were evaluated using Kaplan-Meier methods and compared between different patients using log-rank tests.RESULTSTwenty-one (6.6%) of 320 EGFR mutant samples with additional gene alterations were identified. The most common concurrent gene was PIK3CA mutation (n = 9), followed by EML4-ALK rearrangement (n = 6), HER2 mutation (n = 3), RET rearrangement (n = 1), ROS1 rearrangement (n = 1) and KRAS mutation (n = 1). Patients with single EGFR mutation had a significantly longer progression-free survival than those with concurrent genes (10.9 vs. 6.0 months, P = 0.002). Among the 21 cases, patients with PIK3CA mutation had the longest median progression-free survival (7.6 months), followed by ALK rearrangement (5.0 months) and other gene types (1.2 months). No overall survival difference was found between patients with single EGFR mutation and concurrent gene alterations (21.0 vs.17.6 months, P = 0.17).ConclusionWe demonstrated that concurrent gene alterations occurred in some patients with EGFR mutations. Concurrent gene alterations decreased the efficacy of EGFR-TKIs.

show abstract

Concomitant EGFR mutation and ALK rearrangement in lung adenocarcinoma is more frequent than expected: Report of a case and review of the literature with demonstration of genes alteration into the same tumor cells

Cited by 58 publications

References 21 publications

CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration

CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration

Clinical Validation of a Novel Commercial Reverse Transcription–Quantitative Polymerase Chain Reaction Screening Assay for Detection of ALK Translocations and Amplifications in Non–Small Cell Lung Carcinomas

Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in Chinese patients with non-small cell lung cancer

Contact Info

Product

Resources

About