Dataset Information

Lineage-Independent Tumors in Bilateral Neuroblastoma.

ABSTRACT: Childhood tumors that occur synchronously in different anatomical sites usually represent metastatic disease. However, such tumors can be independent neoplasms. We investigated whether cases of bilateral neuroblastoma represented independent tumors in two children with pathogenic germline mutations by genotyping somatic mutations shared between tumors and blood. Our results suggested that in both children, the lineages that had given rise to the tumors had segregated within the first cell divisions of the zygote, without being preceded by a common premalignant clone. In one patient, the tumors had parallel evolution, including distinct second hits in SMARCA4, a putative predisposition gene for neuroblastoma. These findings portray cases of bilateral neuroblastoma as having independent lesions mediated by a germline predisposition. (Funded by Children with Cancer UK and Wellcome.).

SUBMITTER: Coorens THH

PROVIDER: S-EPMC7611571 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lineage-Independent Tumors in Bilateral Neuroblastoma.

Coorens Tim H H THH Farndon Sarah J SJ Mitchell Thomas J TJ Jain Neha N Lee Sangjin S Hubank Michael M Sebire Neil N Anderson John J Behjati Sam S

The New England journal of medicine 20201101 19

Childhood tumors that occur synchronously in different anatomical sites usually represent metastatic disease. However, such tumors can be independent neoplasms. We investigated whether cases of bilateral neuroblastoma represented independent tumors in two children with pathogenic germline mutations by genotyping somatic mutations shared between tumors and blood. Our results suggested that in both children, the lineages that had given rise to the tumors had segregated within the first cell divisi ...[more]

PMID: 33211929

Similar Datasets

Project description:BackgroundSynchronous tumors can be independent primary tumors or a primary-metastatic (clonal) pair, which may have clinical implications. Mutational profiling of tumor DNA is increasingly common in the clinic. We investigated whether mutational profiling can distinguish independent from clonal tumors in breast and other cancers, using a carefully defined test based on the Clonal Likelihood Score (CLS = 100 x # shared high confidence (HC) mutations/ # total HC mutations).MethodsStatistical properties of a formal test using the CLS were investigated. A high CLS is evidence in favor of clonality; the test is implemented as a one-sided binomial test of proportions. Test parameters were empirically determined using 16,422 independent breast tumor pairs and 15 primary-metastatic tumor pairs from 10 cancer types using The Cancer Genome Atlas.ResultsWe validated performance of the test with its established parameters, using five published data sets comprising 15,758 known independent tumor pairs (maximum CLS = 4.1%, minimum p-value = 0.48) and 283 known tumor clonal pairs (minimum CLS 13%, maximum p-value <0.01), across renal cell, testicular, and colorectal cancer. The CLS test correctly classified all validation samples but one, which it appears may have been incorrectly classified in the published data. As proof-of-concept we then applied the CLS test to two new cases of invasive synchronous bilateral breast cancer at our institution, each with one hormone receptor positive (ER+/PR+/HER2-) lobular and one triple negative ductal carcinoma. High confidence mutations were identified by exome sequencing and results were validated using deep targeted sequencing. The first tumor pair had CLS of 81% (p-value < 10-15), supporting clonality. In the second pair, no common mutations of 184 variants were validated (p-value >0.99), supporting independence. A plausible molecular mechanism for the shift from hormone receptor positive to triple negative was identified in the clonal pair.ConclusionWe have developed the statistical properties of a carefully defined Clonal Likelihood Score test from mutational profiling of tumor DNA. Under identified conditions, the test appears to reliably distinguish between synchronous tumors of clonal and of independent origin in several cancer types. This approach may have scientific and clinical utility.

Project description:Introduction Warthin tumor is described as papillary cystadenoma lymphomatosum and is the second most common tumor of the parotid glands. Bilateral synchronous incidence is rare, occurring in 7 to 10% of the cases. It is more common in males between 60 and 70 years of age and is closely related to smoking. There is slow growth and the condition is a delimited nodule of regular outlines; it has low rates of malignant progression and recurrence. Objective Report a case of synchronous bilateral Warthin tumor occurring in an elderly patient, and review incidence and peculiarities of this tumor. Case Report A 78-year-old man who used to smoke had a history of mild pain in the topography of right parotid three weeks ago. Patient with hypertension, diabetes and a longtime smoker (smoking a pack per day for 32 years) noticed a progressive bulging in the right parotid region for about 2.5 years ago, and noticed another progressive bulging (althought in the left parotid region), for about one year ago. Patient denied fever, redness, skin lesions and pain during this period until last three weeks, when he sought medical attention for a mild pain in the right facial region. The patient underwent cervical magnetic resonance imaging that showed tumor lesions in both parotids. Fine needle aspiration revealed a typical lesion of epithelial oxyphilic cells associated with reactive lymphoid proliferation, suggesting Warthin tumor. The patient underwent two superficial parotidectomies, and the histopathologic result from both tumors of parotid glands showed papillary cystadenoma lymphomatosum. Conclusion The occurrence of synchronous bilateral Warthin tumor is extremely rare, and anamnesis and physical examination, as well as some complementary examinations, are important means for diagnostic evaluation. Confirmation of the diagnosis can only be obtained through a histopathologic study. A superficial or total parotidectomy is the recommended treatment for the disease.

Dataset Information

Lineage-Independent Tumors in Bilateral Neuroblastoma.

Publications

Lineage-Independent Tumors in Bilateral Neuroblastoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets