Considerations for the use of circulating tumor DNA sequencing as a screening tool in cancer predisposition syndromes

Paramathas, Sangeetha; Guha, Tanya; Pugh, Trevor J.; Malkin, David; Villani, Anita

doi:10.1002/pbc.28758

Cited by 6 publications

(2 citation statements)

References 53 publications

(64 reference statements)

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“…Moreover, considering that Burkitt lymphoma appears rather frequent in patients with KS and has a doubling time of approximately 24 h only long-term interval surveillance would not be effective. Alternatively, liquid-biopsy-based surveillance strategies might overcome some of these hurdles in paediatric patients with a cancer predisposition syndrome [ 142 ]. The (epi-)genetic analysis revealed a typical ERMS methylation- and copy number profile.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes

et al. 2022

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Kabuki syndrome is a well-recognized syndrome characterized by facial dysmorphism and developmental delay/intellectual disability and in the majority of patients a germline variant in KMT2D is found. As somatic KMT2D variants can be found in 5–10% of tumors a tumor predisposition in Kabuki syndrome is discussed. So far less than 20 patients with Kabuki syndrome and a concomitant malignancy have been published. Here we report on a female patient with Kabuki syndrome and a c.2558_2559delCT germline variant in KMT2D who developed an embryonal rhabdomyosarcoma (ERMS) at 10 years. On tumor tissue we performed DNA-methylation profiling and exome sequencing (ES). Copy number analyses revealed aneuploidies typical for ERMS including (partial) gains of chromosomes 2, 3, 7, 8, 12, 15, and 20 and 3 focal deletions of chromosome 11p. DNA methylation profiling mapped the case to ERMS by a DNA methylation-based sarcoma classifier. Sequencing suggested gain of the wild-type KMT2D allele in the trisomy 12. Including our patient literature review identified 18 patients with Kabuki syndrome and a malignancy. Overall, the landscape of malignancies in patients with Kabuki syndrome was reminiscent of that of the pediatric population in general. Histopathological and molecular data were only infrequently reported and no report included next generation sequencing and/or DNA-methylation profiling. Although we found no strong arguments pointing towards KS as a tumor predisposition syndrome, based on the small numbers any relation cannot be fully excluded. Further planned studies including profiling of additional tumors and long term follow-up of KS-patients into adulthood could provide further insights.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes

et al. 2022

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“…While ctDNA is still in development, evidence suggests its potential to ll current screening limitations for HCS. Using ctDNA as a cancer screening tool may help tailor clinical management including informing further screening tests, decisions on whether/when to undergo invasive prophylactic surgery and treatment timelines and/or options 10,11 .…”

Section: Introductionmentioning

confidence: 99%

“I just wanted more”: Hereditary cancer syndromes patients’ perspectives on the utility of circulating tumour DNA testing for cancer screening

Bombard

Adi-Wauran²,

Clausen³

et al. 2023

Preprint

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Hereditary cancer syndromes (HCS) predispose individuals to a higher risk of developing multiple cancers. However, current screening strategies have limited ability to screen for all cancer risks. Circulating tumour DNA (ctDNA) detects DNA fragments shed by tumour cells in the bloodstream and can potentially detect cancers early. This study aimed to explore patients’ perspectives on ctDNA’s utility to help inform its clinical adoption and implementation. We conducted a qualitative interpretive description study using semi-structured phone interviews. Participants were purposively sampled adult HCS patients recruited from a Canadian HCS research consortium. Thirty HCS patients were interviewed (n=19 women, age range 20s-70s, n=25 were white). Participants were highly concerned about developing cancers, particularly those without reliable screening options for early detection. They “just wanted more” than their current screening strategies. Participants were enthusiastic about ctDNA’s potential to be comprehensive (detect multiple cancers), predictive (detect cancers early) and tailored (lead to the personalized clinical management). Participants also acknowledged ctDNA’s potential limitations, including false positives/negatives risks and experiencing additional anxiety. However, they saw ctDNA’s potential benefits outweighing its limitations. In conclusion, participants’ belief in ctDNA’s potential to improve their care overshadowed its limitations, indicating patients’ support for using ctDNA in HCS care.

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Screening of cancer predisposition syndromes

Al-Sarhani

Gottumukkala

Grasparil³

et al. 2021

Pediatr Radiol

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Considerations for the use of circulating tumor DNA sequencing as a screening tool in cancer predisposition syndromes

Cited by 6 publications

References 53 publications

Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes

Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes

“I just wanted more”: Hereditary cancer syndromes patients’ perspectives on the utility of circulating tumour DNA testing for cancer screening

Screening of cancer predisposition syndromes

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