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. 2024 Mar;63(3):e23229.
doi: 10.1002/gcc.23229.

Genomic profile analysis of leiomyomas with bizarre nuclei and fumarate hydratase deficient leiomyomas: Strengths, weaknesses, and limitations of array-CGH interpretation

Quitterie Fontanges  1   2   3 , Paul Dubos  4 , Tom Lesluyes  5 , Yec'han Laizet  4 , Valérie Velasco  6 , Bárbara Meléndez  1 , Nicky D'Haene  1 , Esther Oliva  7 , Robert H Young  7 , Laetitia Mayeur  6 , Flora Rebier  6 , Mélissa Alamé  6 , Claire Larmonier  6 , Mojgan Devouassoux-Shisheboran  8 , Laurent Arnould  9 , Isabelle Soubeyran  6 , Camille Chakiba  10 , Anne Floquet  10 , Guillaume Babin  11 , Frédéric Guyon  11 , Eliane Mery  12 , Sophie Le Guellec  12 , Jean-Christophe Noël  1 , Sabrina Croce  6   13 , Frédéric Chibon  5   12
Affiliations

Genomic profile analysis of leiomyomas with bizarre nuclei and fumarate hydratase deficient leiomyomas: Strengths, weaknesses, and limitations of array-CGH interpretation

Quitterie Fontanges et al. Genes Chromosomes Cancer. 2024 Mar.

Abstract

A close relationship has been demonstrated between genomic complexity and clinical outcome in uterine smooth muscle tumors. We studied the genomic profiles by array-CGH of 28 fumarate hydratase deficient leiomyomas and 37 leiomyomas with bizarre nuclei (LMBN) from 64 patients. Follow-up was available for 46 patients (from three to 249 months, mean 87.3 months). All patients were alive without evidence of disease. For 51 array-CGH interpretable tumors the mean Genomic Index (GI) was 16.4 (median: 9.8; from 1 to 57.8), significantly lower than the mean GI in LMS (mean GI 51.8, p < 0.001). We described three groups: (1) a group with FH deletion (24/58) with low GI (mean GI: 11 vs. 22,4, p = 0.02), (2) a group with TP53 deletion (17/58) with higher GI (22.4 vs. 11 p = 0.02), and (3) a group without genomic events on FH or TP53 genes (17/58) (mean GI:18.3; from 1 to 57.8). Because none of these tumors recurred and none showed morphological features of LMS we concluded that GI at the cut-off of 10 was not applicable in these subtypes of LM. By integration of all those findings, a GI <10 in LMBN remains a valuable argument for benignity. Conversely, in LMBN a GI >10 or alteration in tumor suppressor genes, should not alone warrant a diagnosis of malignancy. Nine tumors were tested with Nanocind CINSARC® signature and all were classified in low risk of recurrence. We propose, based on our observations, a diagnostic approach of these challenging lesions.

Keywords: CGH array; fumarate hydratase deficient leiomyoma; genomic index; leiomyoma with bizarre nuclei; uterine smooth muscle tumors.

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References

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