Notochordal tumors

2022-03-02 Paola Dal Cin, PhD , Judith VMG Bovée Affiliation

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.Leiden University Medical Center, Leiden, The Netherlands

Classification

Definition

Chordoma is a rare malignant bone tumor, with a phenotype that recapitulates the notochord and occurs in the axial skeleton of cranial, vertebral, and sacral sites. ^1,2

Notochordal tumors	Genetic marker(s)
Benign notochordal cell tumors	Chromosome gain or normal copy number was more common , while chromosome loss was infrequent ³
Conventional chordoma	Karyotypes, microarray and SNP-array analyses revealed nonrandom copy number losses across the genome, the most fequent been 3p21, 9p21, 10q23 and 22q, while gains are uncommon in chordomas. ^4-7
	Somatic duplications of the notochordal transcription factor brachyury T, TBXT at q27, a transcriptional factor required for notochordal development. ^8,9 In addition, PIK3CA signalling mutations and LYST inactivating mutations, mainly seen in sacral sites. ¹⁰ A common genetic polymorphism , rs2305089, and germline TBXT tandem duplication , associated with an increased risk for both familial and sporadic chordomas. ¹¹ Rare PALB2 and BRCA2 germline variants, whose products play essential roles in homologous recombination (HR) and tumor suppression in sporadic cases ,as well as familiar chordoma case .¹²
	Genomic PBRM1 alterations and homozygous deletions of CDKN2A and CDKN2B are the most prevalent events in skull-chordroma. ⁷ TERT rearrangements are seen in a small subset of cases. ¹³
Dedifferentiated chordoma	See conventional chordoma
Poorly dedifferentiated chordoma	Homozygous SMARCB1 deletions of variable size,that can be detected by FISH analysis, ¹⁴ with sometime co-deletion of EWSR1. ¹⁵ A minority of cases with intact SMARCB1 but with loss SMARCB1 expression. ¹⁶
	Expanding family of SMARCB1-deficient tumors. ^17-20

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	28797506	2017	Notochordal Tumors: An Update on Molecular Pathology with Therapeutic Implications.	Yamaguchi T et al
2	32825957	2020	Chordomas: A review with emphasis on their pathophysiology, pathology, molecular biology, and genetics.	Karpathiou G et al
3	30355586	2019	Benign notochordal cell tumour: clinicopathology and molecular profiling of 13 cases.	Du J et al
4	21602918	2011	Recurrent chromosomal copy number alterations in sporadic chordomas.	Le LP et al
5	24983247	2014	Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1.	Choy E et al
6	27072194	2016	Genomic aberrations frequently alter chromatin regulatory genes in chordoma.	Wang L et al
7	33536423	2021	Whole genome sequencing of skull-base chordoma reveals genomic alterations associated with recurrence and chordoma-specific survival.	Bai J et al
8	16538613	2006	Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas.	Vujovic S et al
9	19801981	2009	T (brachyury) gene duplication confers major susceptibility to familial chordoma.	Yang XR et al
10	29026114	2017	The driver landscape of sporadic chordoma.	Tarpey PS et al
11	24990759	2014	Characterization of T gene sequence variants and germline duplications in familial and sporadic chordoma.	Kelley MJ et al
12	35762214	2022	Rare germline variants in PALB2 and BRCA2 in familial and sporadic chordoma.	Xia B et al
13	34583232	2021	TERT gene rearrangement in chordomas and comparison to other TERT-rearranged solid tumors.	Yoon JY et al
14	29119645	2018	High sensitivity of FISH analysis in detecting homozygous SMARCB1 deletions in poorly differentiated chordoma: a clinicopathologic and molecular study of nine cases.	Owosho AA et al
15	27281413	2016	The contribution of cell cycle to heterogeneity in single-cell RNA-seq data.	McDavid A et al
16	21057957	2010	Loss of SMARCB1/INI1 expression in poorly differentiated chordomas.	Mobley BC et al
17	28109176	2017	Oncogenic roles of SMARCB1/INI1 and its deficient tumors.	Kohashi K et al
18	29280680	2018	SMARCB1-deficient Tumors of Childhood: A Practical Guide.	Pawel BR et al
19	30134255	2018	Diagnostic Immunohistochemistry for Soft Tissue and Bone Tumors: An Update.	Schaefer IM et al
20	33796273	2020	SMARCB1/INI1-deficient tumors of adulthood.	Parker NA et al

External Links

Citation

Paola Dal Cin, PhD ; Judith VMG Bovée

Notochordal tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-02