Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer.
Lips, Esther H Kumar, Tapsi Megalios, Anargyros Visser, Lindy L Sheinman, Michael Fortunato, Angelo Shah, Vandna Hoogstraat, Marlous Sei, Emi Mallo, Diego
Lips, Esther H
Kumar, Tapsi
Megalios, Anargyros
Visser, Lindy L
Sheinman, Michael
Fortunato, Angelo
Shah, Vandna
Hoogstraat, Marlous
Sei, Emi
Mallo, Diego
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2022-06-09
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Abstract
Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers
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Lips EH, Kumar T, Megalios A, Visser LL, Sheinman M, Fortunato A, Shah V, Hoogstraat M, Sei E, Mallo D, Roman-Escorza M, Ahmed AA, Xu M, van den Belt-Dusebout AW, Brugman W, Casasent AK, Clements K, Davies HR, Fu L, Grigoriadis A, Hardman TM, King LM, Krete M, Kristel P, de Maaker M, Maley CC, Marks JR, Menegaz BA, Mulder L, Nieboer F, Nowinski S, Pinder S, Quist J, Salinas-Souza C, Schaapveld M, Schmidt MK, Shaaban AM, Shami R, Sridharan M, Zhang J, Stobart H, Collyar D, Nik-Zainal S, Wessels LFA, Hwang ES, Navin NE, Futreal PA; Grand Challenge PRECISION consortium; Thompson AM, Wesseling J, Sawyer EJ. Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer. Nat Genet. 2022 Jun;54(6):850-860. doi: 10.1038/s41588-022-01082-3. Epub 2022 Jun 9
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Article