Differences of clinical features, prognosis and genetic mutations in Chinese patients with malignant melanoma and additional primary tumours

Abstract

Background: The differences in the clinical features, prognosis and genetic mutations in Chinese patients with malignant melanoma (MM) and additional primary tumours remain unclear.

Methods: A retrospective analysis was conducted on patients with malignancies in Fujian Cancer Hospital from January 2007 to September 2022, end follow-up in September 2023. Clinical data were gathered, survival analysis was performed, and genetic mutations were detected.

Results: There were 58 of 1223 melanoma patients with melanoma and additional primary tumours, an incidence of 4.74%. Acral MM was the most common subtype (26/58), 23 (39.66%) patients had concomitant digestive tumours. Patients who had MM as their first primary tumour (MMFP) had shorter tumour occurrence intervals (9.93 vs. 57.78 months, p = .008) but longer melanoma survival (MM-OS) than the non-MMFP group (100.43 vs. 18.93 months, p = .015). Patients with cancer family histories were more likely to have pathogenic and likely pathogenic (P/LP) mutations (2/5 vs. 4/25). The somatic BRAF gene mutation was frequently observed in MM tissue (8/19, 42.11%). Three patients had whole-genome doubling and microsatellite instability-high (MSI-H). The COSMIC2 signature 3 was significantly higher in the P/LP group.

Conclusions: The frequency of MM and additional primary tumours is about 5% in Chinese populations. Patients with melanoma diagnosed first have longer melanoma survival. Digestive system tumours were the most concomitant; a digestive examination is advisable, especially for those with an expected overall survival (OS) greater than 10 months. Meanwhile, patient's family cancer history should be followed up in detail, along with completion of germline P/LP mutation and somatic mutation testing, all of which may provide valuable support for further treatment.

Keywords: Multiple primary malignant tumours; epidemiology; genetic mutation; melanoma; prognosis.

Figure 1.

Survival differences in patients with melanoma and additional primary tumours. (A) The survival time of malignant melanoma (MM-OS) in MMFP patients and non-MMFP patients. (B) The melanoma-specific survival time (MSS) in MMFP patients and non-MMFP patients. (C) MM-OS in SMPC patients and MMPC patients. (D) MSS in SMPC patients and MMPC patients. (E) MM-OS in patients with or without tumour family histories. (F) MSS in patients with or without tumour family histories. (G) MM-OS in patients with P/LP or non-P/LP germline mutation.

Figure 2.

Difference of germline mutations in patients with melanoma and additional primary tumours. (A) Distributions of germline mutations in patients with melanoma and additional primary tumours. (B) Comparison of germline mutation rates between patients with MM and additional primary tumours and age-matched patients with single primary melanoma.

Figure 3.

Difference of somatic mutations in 19 melanoma tissue samples. (A) Distributions of somatic mutations in 19 melanoma tissue samples. (B) The genomic CNV variation in 19 melanoma tissue samples. (C) Profiles of somatic COSMIC Signatures in 19 melanoma tissue samples. (D) Somatic COSMIC signature 3 was significantly higher in the melanoma tissue samples with P/LP germline mutations. (E) Enrichment genetic pathways in 19 melanoma tissue samples.