Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers

Weinberg, Benjamin A.; Gowen, Kyle; Lee, Thomas K.; Ou, Sai Hong Ignatius; Bristow, Robert G.; Krill, Lauren; Almira-Suarez, M. Isabel; Ali, Siraj M.; Miller, Vincent A.; Liu, Stephen V.; Klempner, Samuel J.

doi:10.1634/theoncologist.2015-0511

Cited by 11 publications

(9 citation statements)

References 38 publications

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“…Specifically, IMTs frequently harbor fusions of the ALK kinase that may be susceptible to ALK inhibitors, well established and approved agents in nonsmall cell lung cancer (4)(5)(6). A complementary role for molecular testing in advanced tumors is established, and comprehensive genomic profiling (CGP) has demonstrated ability to both re-classify tumors and distinguish recurrence from a second primary (7).…”

Section: Introductionmentioning

confidence: 99%

TNS1- ALK Fusion in a Recurrent, Metastatic Uterine Mesenchymal Tumor Originally Diagnosed as Leiomyosarcoma

Lee¹,

Singh

Ali³

et al. 2019

ama

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Objective. We report a female patient diagnosed with a leiomyosarcoma and who harbored a druggable target as identified by comprehensive genomic profiling in the course of clinical care.Case Report. The patient progressed five years after curative intent surgery and adjuvant treatment. After failure of multiple lines of chemotherapy,she was enrolled in a trial of an ALK inhibitor based on comprehensive genomic profiling (CGP) identifying an TNS1-ALK fusion.Conclusion. In this case, identification of the ALK kinase fusion permitted enrollment in a matched mechanism driven clinical trial after exhausting standard of care treatment options. CGP raises the possibility of uterine inflammatory myofibroblastic tumor as an alternative diagnosisto leiomyosarcoma, highlighting the complementary role of CGP beyond immunohistochemical analyses.

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Section: Introductionmentioning

confidence: 99%

TNS1- ALK Fusion in a Recurrent, Metastatic Uterine Mesenchymal Tumor Originally Diagnosed as Leiomyosarcoma

Lee¹,

Singh

Ali³

et al. 2019

ama

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“…Most of these reports have focused on multiple tumors with the same organ, including multiple lung adenocarcinomas, multifocal hepatocellular carcinomas, and bilateral ovarian cancers 17 , 32 , 33 . Some studies have also reported the utilization of the NGS assay for distinguishing metastasis from second primary cancers in patients with multiple tumors from different organs 34 , 35 . However, the application of WES to distinguish SPT from LM in patients with double SCCs of the esophagus and lung has not been described.…”

Section: Discussionmentioning

confidence: 99%

Identification of second primary tumors from lung metastases in patients with esophageal squamous cell carcinoma using whole-exome sequencing

Xue

Fan

et al. 2020

Theranostics

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Esophageal squamous cell carcinoma (ESCC) patients with a synchronous or metachronous lung tumor can be diagnosed with lung metastasis (LM) or a second primary tumor (SPT), but the accurate discrimination between LM and SPT remains a clinical dilemma. This study aimed to investigate the feasibility of using the whole-exome sequencing (WES) technique to distinguish SPT from LM. Methods: We performed WES on 40 tumors from 14 patients, including 12 patients with double squamous cell carcinomas (SCCs) of the esophagus and lung (lymph node metastases were sequenced as internal controls) diagnosed as LM according to pathological information and 2 patients with paired primary ESCC and non-lung metastases examined as external controls. Results: Shared genomic profiles between esophageal (T) and lung (D) tumors were observed in 7 patients, suggesting their clonal relatedness, thus indicating that the lung tumors of these patients should be LM. However, distinct genomic profiles between T and D tumors were observed in the other 5 patients, suggesting the possibility of SPTs that were likely formed through independent multifocal oncogenesis. Conclusions: Our data demonstrate the limitations and insufficiency of clinicopathological criteria and that WES could be useful in understanding the clonal relationships of multiple SCCs.

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“…In addition, there is no particular method established to assess genetic relationships and clonality in primary and metastatic sites in malignancy. However, limited studies have shown the potential of genetic profiling to distinguish between a metastatic recurrence of the primary cancer and newly developed second primary cancer in several malignancies[6-8]. Previous reports demonstrated shared genomic alteration in paired primary and metastatic sites was useful in differentiating multifocal non-small cell lung cancer from intrapulmonary metastasis[7,8].…”

Section: Discussionmentioning

confidence: 99%

“…The histological differentiation between primary ICA and liver metastasis of GBC is often difficult owing to morphological and immunohistochemical resemblance, whereas the distinction between the metastasis of the primary malignancy and newly developed second primary malignancy is clinically important for accurate staging and tailoring treatment strategies[5]. Reflecting recent technical advances in high-throughput next-generation sequencing, there are several reports describing the utility of genomic profiling in the differential diagnosis of a metastatic recurrence and distinguishing it from second primary malignancy[6].…”

Section: Introductionmentioning

confidence: 99%

Gallbladder cancer harboring ERBB2 mutation on the primary and metastatic site: A case report

Inagaki

Maeda

Kimura

et al. 2019

WJGO

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BACKGROUNDBile duct cancer constitutes gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICA), and extrahepatic cholangiocarcinoma (ECA). These three entities show morphological and immunohistochemical resemblance so that it is difficult to differentiate between primary ICA and liver metastasis of GBC, which sometimes becomes a point of discussion in clinical practice. Although these cancers demonstrate significant differences in their mutational landscape, several reports demonstrated shared genomic alteration in paired primary and metastatic site aids in distinguishing metastatic recurrence from second primary cancers.CASE SUMMARYWe present a 73-year-old female patient who underwent curative resection for GBC harboring epidermal growth factor receptor 2 (ERBB2) activating mutation on next-generation sequencing (NGS)-based genomic testing. One year later, a hepatic lesion was observed on follow-up imaging and she underwent surgical resection for a pathological diagnosis. The histological findings of the hepatic lesion were similar to those of the primary lesion. Additionally, using NGS panel testing, the hepatic lesion was found to have ERBB2 activating mutation, which is the identical mutation detected in the sequencing result of the primary site. ERBB2 activating mutation occurs more frequently in GBC than ICA and ECA. Therefore, in the present case, we think this molecular finding potentiated the diagnosis of the liver mass toward a metastatic recurrence. Additionally, this patient underwent HER2-targeted treatment with lapatinib in combination with capecitabin and obtained clinical benefit.CONCLUSIONThis case illustrated NGS panel usefulness in distinguishing GBC recurrence from second primary cancer and HER2-targeted agent efficacy on ERBB2 mutated GBC.

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Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers

Cited by 11 publications

References 38 publications

TNS1- ALK Fusion in a Recurrent, Metastatic Uterine Mesenchymal Tumor Originally Diagnosed as Leiomyosarcoma

TNS1- ALK Fusion in a Recurrent, Metastatic Uterine Mesenchymal Tumor Originally Diagnosed as Leiomyosarcoma

Identification of second primary tumors from lung metastases in patients with esophageal squamous cell carcinoma using whole-exome sequencing

Gallbladder cancer harboring ERBB2 mutation on the primary and metastatic site: A case report

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