Targeted Next-Generation Sequencing Reveals Exceptionally High Rates of Molecular Driver Mutations in Never-Smokers with Lung Adenocarcinoma

Essential thrombocythaemia (ET) is driven by somatic mutations involving the JAK2, CALR and MPL genes. Approximately 10% of patients lack driver mutations and are referred as ‘triple-negative’ ET (TN-ET). The diagnosis of TN-ET, however, relies on bone marrow examination that is not always performed in routine practice, and thus in the real-world setting, there are a group of cases with suspected TN-myeloproliferativeneoplasm.In this real-world cohort, patients with suspected TN-ET were initially rescreened for JAK2, CALR and MPL and then targeted next-generation sequencing (NGS) was applied.The 35 patients with suspected TN-ET had a median age at diagnosis of 43 years (range 16–79) and a follow-up of 10 years (range 2–28). The median platelet count was 758×109/L (range 479–2903). Thrombosis prior to and following diagnosis was noted in 20% and 17% of patients. Six patients were JAK2V617F and two patients were CALR positive on repeat screening. NGS results showed that 24 of 27 patients harboured no mutations. Four mutations were noted in three patients.There was no evidence of clonality for the majority of patients with suspected TN-ET with targeted NGS analysis. Detection of driver mutations in those who were previously screened suggests that regular rescreening is required. This study also questions the diagnosis of TN-ET without the existence of a clonal marker.

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Routine molecular testing of resected early-stage lung adenocarcinoma with targeted next-generation sequencing demonstrates a high rate of actionable mutations

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2015.12.075 ◽

2016 ◽

Vol 11 (2) ◽

pp. S44-S45 ◽

Cited By ~ 1

Author(s):

Brendon M. Stiles ◽

Abu Nasar ◽

Mohamed Kamel Hussein ◽

Galal Rafik Ghaly ◽

Mohamed Rahouma Ahmed ◽

...

Keyword(s):

Next Generation Sequencing ◽

Lung Adenocarcinoma ◽

Early Stage ◽

High Rate ◽

Molecular Testing ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Generation Sequencing

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Synchronous Pulmonary Adenocarcinomas

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa023 ◽

2020 ◽

Vol 154 (1) ◽

pp. 57-69

Author(s):

Carlos A Pagan ◽

Catherine A Shu ◽

John P Crapanzano ◽

Galina G Lagos ◽

Mark B Stoopler ◽

...

Keyword(s):

Next Generation Sequencing ◽

Gene Panel ◽

Driver Mutations ◽

Molecular Testing ◽

Next Generation ◽

Synchronous Tumors ◽

Targeted Next Generation Sequencing ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

Abstract Objectives To determine concordance/discordance between morphology and molecular testing (MT) among synchronous pulmonary carcinomas using targeted next generation sequencing (NGS), with and without comprehensive molecular review (CMR), vs analyses of multiple singe genes (non-NGS). Methods Results of morphologic and MT assessment were classified as concordant, discordant, or indeterminate. For discordant cases, comprehensive histologic assessment (CHA) was performed. Results Forty-seven cases with 108 synchronous tumors were identified and underwent MT (NGS, n = 23 and non-NGS, n = 24). Histology and MT were concordant, discordant, and indeterminate in 53% (25/47), 21% (10/47), and 26% (12/47) of cases, respectively. CHA of the 10 discordant cases revised results of three cases. Conclusions There is discordance between histology and MT in a subset of cases and MT provides an objective surrogate for staging synchronous tumors. A limited gene panel is sufficient for objectively assessing a relationship if the driver mutations are distinct. Relatedness of mutations require CMR with a larger NGS panel (eg, 50 genes).

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Abstract 573: Mutations found by targeted next generation sequencing is associated with intra-tumor immune profile and may predict response to anti-PD1 therapy in lung adenocarcinoma

10.1158/1538-7445.am2019-573 ◽

2019 ◽

Author(s):

Audrey Lupo ◽

Jerome Biton ◽

Marco Alifano ◽

Diane Damotte ◽

Jennifer Arrondeau ◽

...

Keyword(s):

Next Generation Sequencing ◽

Lung Adenocarcinoma ◽

Next Generation ◽

Immune Profile ◽

Targeted Next Generation Sequencing ◽

Generation Sequencing

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Abstract 573: Mutations found by targeted next generation sequencing is associated with intra-tumor immune profile and may predict response to anti-PD1 therapy in lung adenocarcinoma

10.1158/1538-7445.sabcs18-573 ◽

2019 ◽

Author(s):

Audrey Lupo ◽

Jerome Biton ◽

Marco Alifano ◽

Diane Damotte ◽

Jennifer Arrondeau ◽

...

Keyword(s):

Next Generation Sequencing ◽

Lung Adenocarcinoma ◽

Next Generation ◽

Immune Profile ◽

Targeted Next Generation Sequencing ◽

Generation Sequencing

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Targeted Next-Generation Sequencing Analysis for Recurrence in Early-Stage Lung Adenocarcinoma

Annals of Surgical Oncology ◽

10.1245/s10434-020-09276-x ◽

2020 ◽

Cited By ~ 1

Author(s):

In Ae Kim ◽

Jae Young Hur ◽

Hee Joung Kim ◽

Jung Hoon Park ◽

Jae Joon Hwang ◽

...

Keyword(s):

Next Generation Sequencing ◽

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Early Stage ◽

Genetic Alterations ◽

Smoking History ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Targeted Ngs ◽

Generation Sequencing

Abstract Background Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20–50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify genetic alterations that can predict recurrence, by comparing the molecular profiles of patient groups with and without recurrence. Methods Tissues from 230 patients with resected stage I–II lung adenocarcinoma (median follow-up: 49 months) were analyzed via targeted NGS for 207 cancer-related genes. The recurrence-free survival according to the number and type of mutation was estimated using the Kaplan–Meier method. Independent predictive biomarkers related to recurrence were identified using the Cox proportional hazards model. Results Recurrence was observed in 64 patients (27.8%). In multivariate analysis adjusted for age, sex, smoking history, stage, surgical mode, and visceral pleural invasion, the CTNNB1 mutation and fusion genes (ALK, ROS1, RET) were negative prognostic factors for recurrence in early-stage lung adenocarcinoma (HR 4.47, p = 0.001; HR 2.73, p = 0.009). EGFR mutation was a favorable factor (HR 0.51, p = 0.016), but the CTNNB1/EGFR co-mutations were negative predictors (HR 19.2, p < 0.001). TP53 mutation was a negative predictor compared with EGFR mutation for recurrence (HR 5.24, p = 0.02). Conclusions: Targeted NGS can provide valuable information to predict recurrence and identify patients at high recurrence risk, facilitating selection of the treatment strategy among close monitoring and adjuvant-targeted therapy. Larger datasets are required to validate these findings.

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