PMC8249865_01
The therapeutic procedure and response of the patient. Panel (A) the flowchart shows the timeline of therapeutic regimes, duration of therapy and patient response. Types of therapies are highlighted in different colors. Blue: chemotherapy; Yellow: surgery; Green: immunotherapy. Panel (B) from left to right, the CT images show the primary cancer lesion at the 9th rib, the right lower lobe metastasis, the right upper lobe metastasis, and the 11th rib metastasis. Arrows indicate the lesions. The HE-stained images were also shown for the three metastases. The HE stained images for the primary cancer tissue was not available due to inaccessible biopsy. Panel (C) from left to right, the CT images show the status of right 9th rib, right lung lower lobe, right lung upper lobe and right 11th rib at May, 2020. EPI, epirubicin; DDP, cisplatin; SPN, solitary pulmonary nodule; THP, pirarubicin; HD-MTX, high-dose methotrexate; PLD, pegylated liposomal doxorubicin; IFO, ifosphamide; GEM, gemcitabine; TXT, taxotere. Details of chemotherapy and immunotherapy can be found in 
Supplementary Table 1
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Here we describe a 29-year-old female patient presenting 9th rib bone destruction, peripheral tissue swelling and solitary pulmonary nodule (SPN) at the right lung lower lobe at the first visit in May 2015 ( Figures 1A, B  ). A new SPN at the right superior lobe and a suspected relapse at the right 11th rib were observed ( Figure 1B ). Immunotherapy with pembrolizumab (100 mg q3w) was therefore started (January 2018), and the patient remained with continuous remission until the last follow-up in May 2020 ( Figure 1C ).
The mutational and copy number alterations for primary and metastatic lesions. The left figure of panel (A) shows the SNV/INDEL mutations of all lesions, and compared the common and exclusive mutations. The right figure of panel (A) shows the distribution and ratio of six types of base changes in the primary and metastatic lesions. Panel (B) shows the full profile of CNV alterations for all lesions (row 1-4) and exclusive CNV lesions for all lesions (row 5-8). Row 9 shows the common Amp/Del alterations from all lesions.
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It can be observed from  Figure 2A  that a couple of mutations overlapped across the lesions, including DPP6 and MUC4, while large amount of mutations did not overlap between the rib lesions and the lung lesions. Analysis of base change distribution shows big difference across the lesions ( Figure 2A ), especially the C>T/T>A base change (brown), which appeared to vary greatly across the four lesions. The CNV changes also showed substantial variation ( Figure 2B ).
The summary of GO (A) and KEGG (B) enrichment. Primary and metastatic lesions with significant enrichment were shown. Significant variation in enrichment was observed among the lesions.
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The pathway enrichment analysis showed similar trend. The majority of GO enrichment was found in the 9th rib primary lesion and the right lung inferior lobe metastasis, which had very little overlap in enrichment, while the other two lesions showed few or no enrichment ( Figure 3A ). In contrast, KEGG enrichment was found in the 9th rib primary lesion, the 11th rib metastasis, and the right lung inferior lobe metastasis, which also had little overlap in enrichment, while no significant enrichment was found with the right lung superior lobe metastasis ( Figure 3B ).